Supramolecular Assembly of Triterpenoids: Current State and Biomedical Perspectives

Jie Zhong , Juan C. Mareque-Rivas , Xinmiao Lan , Yu-Xiong Su

Aggregate ›› 2025, Vol. 6 ›› Issue (8) : e70081

PDF
Aggregate ›› 2025, Vol. 6 ›› Issue (8) : e70081 DOI: 10.1002/agt2.70081
REVIEW

Supramolecular Assembly of Triterpenoids: Current State and Biomedical Perspectives

Author information +
History +
PDF

Abstract

Triterpenoids exhibit remarkable pharmacological characteristics and have garnered significant research attention, owing to their unique backbone structures and numerous modification sites. Recent advancements in supramolecular chemistry have highlighted the potential of triterpenoids to form organized assemblies through noncovalent interactions, affording versatile functional properties. By leveraging their unique structural characteristics and biological activities, innovative strategies can be developed to enhance the efficacy and safety of biomedical therapies. This review describes the recent advances in triterpenoids serving as (i) functional groups for aggregation-induced emission, (ii) building blocks for self-transportation and drug delivery, (iii) potential gelators for rational hydrogel design, and (iv) cholesterol alternatives for optimizing lipid-based nanoparticles. The biomedical perspectives of triterpenoid-based supramolecular assemblies and potential bottlenecks in clinical translation are also discussed, with the hope of offering insights into future research and biomedical applications.

Keywords

hydrogels / nanotheranostics / natural products / supramolecular assembly / triterpenoids

Cite this article

Download citation ▾
Jie Zhong, Juan C. Mareque-Rivas, Xinmiao Lan, Yu-Xiong Su. Supramolecular Assembly of Triterpenoids: Current State and Biomedical Perspectives. Aggregate, 2025, 6(8): e70081 DOI:10.1002/agt2.70081

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

A. Eschenmoser, L. Ruzicka, O. Jeger, and D. Arigoni, “Zur Kenntnis der Triterpene. 190. Mitteilung. Eine stereochemische Interpretation der biogenetischen Isoprenregel bei den Triterpenen,” Helvetica Chimica Acta 38, no. 7 (1955): 1890-1904.

[2]

A. Eschenmoser and D. Arigoni, “Revisited After 50 Years: The ‘Stereochemical Interpretation of the Biogenetic Isoprene Rule for the Triterpenes’,” Helvetica Chimica Acta 88, no. 12 (2005): 3011-3050.

[3]

Z. Özdemir, Nonappa, and Z. Wimmer, “Triterpenoid Building Blocks for Functional Nanoscale Assemblies: A Review,” ACS Applied Nano Materials 5, no. 11 (2022): 16264-16277.

[4]

B. G. Bag and R. Majumdar, “Self-Assembly of Renewable Nano-Sized Triterpenoids,” Chemical Record 17, no. 9 (2017): 841-873.

[5]

H. Zhang, J. Guo, J. Hu, and M. Zhou, “Terpenoid-Based Supramolecular Materials: Fabrications, Performances, Applications,” Supramolecular Chemistry 34, no. 2 (2023): 105-131.

[6]

B. G. Bag, C. Garai, R. Majumdar, and M. Laguerre, “Natural Triterpenoids as Renewable Nanos,” Structural Chemistry 23, no. 2 (2012): 393-398.

[7]

B. G. Bag, G. C. Maity, and S. R. Pramanik, “Arjunolic Acid: A Promising New Building Block for Nanochemistry,” Pramana 65, no. 5 (2005): 925-929.

[8]

B. G. Bag, S. K. Dinda, P. P. Dey, V. A. Mallia, and R. G. Weiss, “Self-Assembly of Esters of Arjunolic Acid Into Fibrous Networks and the Properties of Their Organogels,” Langmuir 25, no. 15 (2009): 8663-8671.

[9]

J. Hu, M. Zhang, and Y. Ju, “A Simple Oleanlic Acid Derivative as Potent Organogelator,” Soft Matter 5, no. 24 (2009): 4971.

[10]

J. Lu, Y. Gao, J. Wu, and Y. Ju, “Organogels of Triterpenoid-Tripeptide Conjugates: Encapsulation of Dye Molecules and Basicity Increase Associated With Aggregation,” RSC Advances 3, no. 45 (2013): 23548.

[11]

J. Lu, J. Wu, and Y. Ju, “Tuning the Aggregation Mode to Induce Different Chiralities in Organogels of Mono- and Bis-Triterpenoid Derivatives and the Preparation of Gold Nanoparticles for Use as a Template,” New Journal of Chemistry 38, no. 12 (2014): 6050-6056.

[12]

P. Dzubak, M. Hajduch, D. Vydra, et al., “Pharmacological Activities of Natural Triterpenoids and Their Therapeutic Implications,” Natural Product Reports 23, no. 3 (2006): 394.

[13]

T. Moses, J. Pollier, J. M. Thevelein, and A. Goossens, “Bioengineering of Plant (tri)Terpenoids: From Metabolic Engineering of Plants to Synthetic Biology in Vivo and in Vitro,” New Phytologist 200, no. 1 (2013): 27-43.

[14]

S. G. Hillier and R. Lathe, “Terpenes, Hormones and Life: Isoprene Rule Revisited,” Journal of Endocrinology 242, no. 2 (2019): R9-R22.

[15]

J. M. Augustin, V. Kuzina, S. B. Andersen, and S. Bak, “Molecular Activities, Biosynthesis and Evolution of Triterpenoid Saponins,” Phytochemistry 72, no. 6 (2011): 435-457.

[16]

X. Lin, X. Huang, W. Pi, et al., “Self-assembly Variation of Glycyrrhetinic Acid Epimers: Assembly Mechanism and Antibacterial Efficacy Between 18 α-GA and 18 β-GA,” Colloids and Surfaces B 242 (2024): 114120.

[17]

B. G. Bag and R. Majumdar, “Self-Assembly of a Renewable Nano-Sized Triterpenoid 18β-Glycyrrhetinic Acid,” RSC Advances 2, no. 23 (2012): 8623-8626.

[18]

B. C. Stephenson, A. Goldsipe, and D. Blankschtein, “Molecular Dynamics Simulation and Thermodynamic Modeling of the Self-Assembly of the Triterpenoids Asiatic Acid and Madecassic Acid in Aqueous Solution,” Journal of Physical Chemistry B 112, no. 8 (2008): 2357-2371.

[19]

J. Liu, “Oleanolic Acid and Ursolic Acid: Research Perspectives,” Journal of Ethnopharmacology 100, no. 1 (2005): 92-94.

[20]

L. Fan, B. Zhang, A. Xu, et al., “Carrier-Free, Pure Nanodrug Formed by the Self-Assembly of an Anticancer Drug for Cancer Immune Therapy,” Molecular Pharmaceutics 15, no. 6 (2018): 2466-2478.

[21]

Z. Li, Y. Zheng, H. Shi, et al., “Convenient Tuning of the Elasticity of Self-Assembled Nano-Sized Triterpenoids to Regulate Their Biological Activities,” ACS Applied Materials & Interfaces 13, no. 37 (2021): 44065-44078.

[22]

X. Zhao, H. Zhang, Y. Gao, Y. Lin, and J. Hu, “A Simple Injectable Moldable Hydrogel Assembled From Natural Glycyrrhizic Acid With Inherent Antibacterial Activity,” ACS Applied Bio Materials 3, no. 1 (2020): 648-653.

[23]

Z. Sun, Y. Hou, X. Xu, et al., “A Novel Nonreversible Heat-Induced Low-Molecular-Weight Gel Based on Naturally-Occurring Self-Assembled Fupenzic Acid for Tumor Therapy,” Colloids and Surfaces B 228 (2023): 113392.

[24]

J. Lu, X. Wu, L. Liu, H. Chen, and Y. Liang, “First Organogelation Study of Ursolic Acid, a Natural Ursane Triterpenoid,” Chemistry Letters 45, no. 8 (2016): 860-862.

[25]

Y. Liu, H. Zhang, X.-W. Chen, T. Yang, C. Sun, and S.-D. Sun, “Fabrication and Characterization of Novel Thermoresponsive Emulsion Gels and Oleogels Stabilizied by Assembling Nanofibrous From Dual Natural Triterpenoid Saponins,” Food Chemistry: X 18 (2023): 100751.

[26]

X.-W. Chen, H. Zhang, X.-X. Li, and S.-D. Sun, “Edible HIPE-Gels and Oleogels Formed by Synergistically Combining Natural Triterpenoid Saponin and Citrus Dietary fiber,” Carbohydrate Polymers 305 (2023): 120499.

[27]

S. Li, P. Li, Y. Chen, et al., “Camellia Saponin Based Oleogels by Emulsion-Templated Method: Preparation, Characterization, and in Vitro Digestion,” ACS Food Science & Technology 3, no. 12 (2023): 2085-2093.

[28]

L. Du, S. Zhou, Y. Huang, and Z. Meng, “Investigation on the Structure Characteristics, Stability Evaluation, and Oral Tribology of Natural Oleanolic Acid-Based Water-in-Oil High Internal Phase and Multiple Pickering Emulsions as Realistic Fat Analogues,” Food Chemistry 465 (2025): 142121.

[29]

E. M. Ahmed, “Hydrogel: Preparation, Characterization, and Applications: A Review,” Journal of Advanced Research 6, no. 2 (2015): 105-121.

[30]

A. S. Hoffman, “Hydrogels for Biomedical Applications,” Advanced Drug Delivery Reviews 64 (2012): 18-23.

[31]

H. Zhang, W. Jianqiao, G. Junbo, and J. Hu, “Natural Terpenoid-Based Sustainable Thermoplastics, Cross-Linked Polymers, and Supramolecular Materials,” Polymer Reviews 64, no. 1 (2024): 119-161.

[32]

W. Teng, Z. Zhou, J. Cao, and Q. Guo, “Recent Advances of Natural Pentacyclic Triterpenoids as Bioactive Delivery System for Synergetic Biological Applications,” Foods 13, no. 14 (2024): 2226.

[33]

Y. Chen, J. W. Y. Lam, R. T. K. Kwok, B. Liu, and B. Z. Tang, “Aggregation-Induced Emission: Fundamental Understanding and Future Developments,” Materials Horizons 6, no. 3 (2019): 428-433.

[34]

X. Yu, Y. Meng, H. Zhang, et al., “Trans/Cis-Stereoisomers of Triterpenoid-Substituted Tetraphenylethene: Aggregation-Induced Emission, Aggregate Morphology, and Mechano-Chromism,” Nanoscale 13, no. 36 (2021): 15257-15266.

[35]

X. Yu, J. Li, H. Zhang, M.-H. Li, and J. Hu, “Glycyrrhetinic Acid and Polyethylene Glycol-Disubstituted Trans/Cis-Tetraphenylethene Stereoisomers Showing Thermoresponsive Fluorescent Self-Assembly,” ACS Applied Polymer Materials 5, no. 9 (2023): 7467-7476.

[36]

X. Wang, X. Zhang, G. Zheng, et al., “Mitochondria-Targeted Pentacyclic Triterpene NIR-AIE Derivatives for Enhanced Chemotherapeutic and Chemo-Photodynamic Combined Therapy,” European Journal of Medicinal Chemistry 264 (2024): 115975.

[37]

B. Zhang, X. Yu, J. Li, K. Wei, L. Gao, and J. Hu, “Four-Armed Biobased Glycyrrhizic Acid-Tailored AIE Fluorescent Gelator,” Journal of Molecular Structure 1258 (2022): 132684.

[38]

J. Liu, F. Yin, J. Hu, and Y. Ju, “Isomerism and Silver Ion-Regulated Triterpenoid-Based Nanostructures for in Situ Synthesis of Ag Nanoparticles With Plasmonic Chirality,” ACS Applied Nano Materials 5, no. 8 (2022): 10735-10743.

[39]

Y. Gao, J. Hao, J. Liu, et al., “Imprinting Supramolecular Chirality on Silica From Natural Triterpenoid-Regulated Helical Ribbons,” Materials Chemistry Frontiers 3, no. 2 (2019): 308-313.

[40]

F. Han, F. Shi, H. Li, Y. Yang, and Y. Li, “Facile Fabrication of Helical Hybrid Silica Ribbons With High-Efficiency Circularly Polarized Luminescence,” Materials Letters 327 (2022): 133026.

[41]

Y. Meng, Z. Li, C. Xie, et al., “Natural Triterpenoid-Tailored Self-Assembled Chiral Helical Ribbons for Regulating Droplet Bounce,” Cell Reports Physical Science 3, no. 4 (2022): 100810.

[42]

J. Mei, Y. Hong, J. W. Lam, A. Qin, Y. Tang, and B. Z. Tang, “Aggregation-Induced Emission: The Whole Is More Brilliant Than the Parts,” Advanced Materials 26, no. 31 (2014): 5429-5479.

[43]

C. Zhang, S. Cheng, Q. Zhuang, A. Xie, and W. Dong, “18α-Glycyrrhetinic Acid Aggregation-Induced Emission Probes for Visual Fluorescence Detection of Explosive as Well Multi-Functional Applications,” New Journal of Chemistry 46, no. 4 (2022): 1896-1904.

[44]

Y. Xiao, A. Ouyang, L. Fan, et al., “Precision Delivery of Binary Cooperative Nanodrugs Self-Assembled by Berberine Glycyrrhetinic Acid Salts for Hepatocellular Carcinoma Treatment,” ACS Applied Materials & Interfaces 16, no. 43 (2024): 58489-58505.

[45]

J. Sun, C. Lv, T. Zhang, J. Zang, and G. Zhao, “Sprayable, Washable, and Light-Perceptible Hydrogels With AIE Activity Constructed by Co-assembly of Natural Glycyrrhizic Acid and Berberine for Fruit Preservation,” Food Chemistry 467 (2025): 142260.

[46]

B. G. Bag, S. N. Hasan, S. Ghorai, and S. K. Panja, “First Self-Assembly of Dihydroxy Triterpenoid Maslinic Acid Yielding Vesicles,” ACS Omega 4, no. 4 (2019): 7684-7690.

[47]

B. G. Bag and K. Paul, “Vesicular and Fibrillar Gels by Self-Assembly of Nanosized Oleanolic Acid,” Asian Journal of Organic Chemistry 1, no. 2 (2012): 150-154.

[48]

B. G. Bag, S. Das, S. N. Hasan, and A. Chandan Barai, “Nanoarchitectures by Hierarchical Self-Assembly of Ursolic Acid: Entrapment and Release of Fluorophores Including Anticancer Drug Doxorubicin,” RSC Advances 7, no. 29 (2017): 18136-18143.

[49]

B. G. Bag and S. S. Dash, “Hierarchical Self-Assembly of a Renewable Nanosized Pentacyclic Dihydroxy-Triterpenoid Betulin Yielding Flower-Like Architectures,” Langmuir 31, no. 51 (2015): 13664-13672.

[50]

S. N. Hasan, J. Banerjee, S. Patra, et al., “Self-Assembled Renewable Nano-Sized Pentacyclic Triterpenoid Maslinic Acids in Aqueous Medium for Anti-Leukemic, Antibacterial and Biocompatibility Studies: An Insight Into Targeted Proteins-Compound Interactions Based Mechanistic Pathway Prediction Through Molecular Docking,” International Journal of Biological Macromolecules 245 (2023): 125416.

[51]

X. Gao, X. Tang, Z. Tu, et al., “Tertiary Amine Modification Enables Triterpene Nanoparticles to Target the Mitochondria and Treat Glioblastoma via Pyroptosis Induction,” Biomaterials 317 (2025): 123035.

[52]

M. Vágvölgyi, E. Kocsis, B. A. Tayeb, et al., “Ecdysteroid-Containing Squalenoylated Self-Assembling Nanoparticles Exert Tumor-Selective Sensitization to Reactive Oxygen Species (ROS)-Induced Oxidative Damage While Protecting Normal Cells: Implications for Selective Radiotherapy,” Journal of Medicinal Chemistry 68, no. 7 (2025): 7197-7212.

[53]

F. Yin, Q. Liu, J. Hu, and Y. Ju, “Natural Oleanolic Acid-Tailored Eutectogels Featuring Multienvironment Shape Memory Performance,” ACS Applied Materials & Interfaces 16, no. 5 (2024): 6424-6432.

[54]

T. Tong, H. Hu, J. Zhou, et al., “Glycyrrhizic-Acid-Based Carbon Dots With High Antiviral Activity by Multisite Inhibition Mechanisms,” Small 16, no. 13 (2020): e1906206.

[55]

C.-M. Lai, J. Xu, B.-C. Zhang, S.-H. He, and J.-W. Shao, “A Natural Product-Derived Nanozyme Regulator Induced Chemo-Ferroptosis Dual Therapy in Remodeling of the Tumor Immune Microenvironment of Hepatocellular Carcinoma,” Chemical Engineering Journal 482 (2024): 148976.

[56]

L. Tian, H. Ji, W. Wang, et al., “Mitochondria-Targeted Pentacyclic Triterpenoid Carbon Dots for Selective Cancer Cell Destruction via Inducing Autophagy, Apoptosis, as Well as Ferroptosis,” Bioorganic Chemistry 130 (2023): 106259.

[57]

S. Zhang, B. Li, J. Zhou, et al., “Kill Three Birds With One Stone: Mitochondria-Localized Tea Saponin Derived Carbon Dots With AIE Properties for Stable Detection of HSA and Extremely Acidic pH,” Food Chemistry 405 (2023): 134865.

[58]

Y. Jiang, L. Xiao, J. Wang, et al., “Carbon Nanodots Constructed by Ginsenosides and Their High Inhibitory Effect on Neuroblastoma,” Journal of Nanobiotechnology 21, no. 1 (2023): 244.

[59]

J. Wang, N. Tian, T. Tian, et al., “Low Toxicity Ginsenoside Rg1-Carbon Nanodots as a Potential Therapeutic Agent for Human Non-Small Cell Lung Cancer,” Colloids and Surfaces B 246 (2025): 114392.

[60]

J. Wang, E. Xu, H. Wang, et al., “Carbon Nanodots-Integrated Multifunctional Nanomedicine Establishes a Regenerative Feedback Loop Between Vascular-Immune-Muscle Systems for Comprehensive Therapy of Critical Limb Ischemia,” ACS Applied Materials & Interfaces 17, no. 17 (2025): 24977-24993.

[61]

P. Sheng, C. Bu, T. Hui, L. Zhou, H. Chen, and G. Zhou, “Polydopamine-Activated Celastrol Carbon Dots for Synergistic Chemotherapy-Photothermal Therapy of Tumors,” International Journal of Pharmaceutics: X 6 (2023): 100218.

[62]

J. Zhong, G. He, X. Ma, et al., “Triterpene-Based Prodrug for Self-Boosted Drug Release and Targeted Oral Squamous Cell Carcinoma Chemotherapy,” ACS Applied Materials & Interfaces 16, no. 32 (2024): 41960-41972.

[63]

X. Yang, C. Ma, Z. Chen, et al., “Single Small Molecule-Assembled Nanoparticles Mediate Efficient Oral Drug Delivery,” Nano Research 12, no. 10 (2019): 2468-2476.

[64]

M. Lin, D. Liu, Y. Gong, et al., “Bioactive Assembly Cofactor-Assisted Ursolic Acid Helix for Enhanced Anticancer Efficacy via in Situ Virus-Like Transition,” Journal of the American Chemical Society 147 (2025): 17010-17021.

[65]

W. Zhang, Y. Huang, J. Li, et al., “Carrier-Free Poly(glycyrrhetinic acid)-Facilitated Celastrol-Loaded Nanoparticle for High-Efficiency Low-Toxicity Treatment of Rheumatoid Arthritis,” Materials and Design 241 (2024): 112951.

[66]

S. Zuo, J. Wang, X. An, Z. Wang, X. Zheng, and Y. Zhang, “Fabrication of Ginsenoside-Based Nanodrugs for Enhanced Antitumor Efficacy on Triple-Negative Breast Cancer,” Frontiers in Bioengineering and Biotechnology 10 (2022): 945472.

[67]

J. Wang, H. Zhao, W. Qiao, J. Cheng, Y. Han, and X. Yang, “Nanomedicine-Cum-Carrier by Co-Assembly of Natural Small Products for Synergistic Enhanced Antitumor With Tissues Protective Actions,” ACS Applied Materials & Interfaces 12, no. 38 (2020): 42537-42550.

[68]

Y. Han, X. Yang, S. Fu, et al., “Co-assembly of Abietic Acid and Oleanolic Acid Into Nanoparticles Encapsulating Proanthocyanidin B2 to Improve Pac B2 Bioavailability and Thermal Stability,” Food Chemistry 485 (2025): 144512.

[69]

L. Zong, Y. Dai, J. Xu, et al., “Luteolin and Glycyrrhetinic Exert Cooperative Effect on Liver Cancer by Selfassembling Into Carrier-Free Nanostructures,” Chinese Chemical Letters (2025): 111325.

[70]

G. You, T. Feng, G. Zhang, et al., “Preparation, Optimization, Characterization and in Vitro Release of Baicalein-Solubilizing Glycyrrhizic Acid Nano-Micelles,” International Journal of Pharmaceutics 601 (2021): 120546.

[71]

G. Li, Z. Song, Y. Ru, et al., “Small-Molecule Nanoprodrug With High Drug Loading and EGFR, PI3K/AKT Dual-Inhibiting Properties for Bladder Cancer Treatment,” Exploration 3, no. 5 (2023): 20220141.

[72]

S. Liu, J. Zhang, R. Fu, et al., “Improved Stability and Aqueous Solubility of β-Carotene via Encapsulation in Self-assembled Bioactive Oleanolic Acid Nanoparticles,” Food Chemistry 373, no. Pt B (2022): 131498.

[73]

C. Liu, W. Du, L. Zhang, and J. Wang, “Natural Synergy: Oleanolic Acid-Curcumin Co-assembled Nanoparticles Combat Osteoarthritis,” Colloids and Surfaces B 245 (2025): 114286.

[74]

Y. Su, R. Chen, B. Wang, et al., “Erythrocyte Membrane Camouflaged Celastrol and Bilirubin Self-Assembly for Rheumatoid Arthritis Immunotherapy Based on STING Inhibition and RONS Clearance,” Journal of Nanobiotechnology 23, no. 1 (2025): 318.

[75]

T. Liang, Y. Wu, Q. Zeng, et al., “Development of a Self-Assembled Micelles Based on Cryptotanshinone and Glycyrrhizic Acid: An Efficient Strategy for Acne Treatment,” International Journal of Pharmaceutics 674 (2025): 125411.

[76]

J. Cui, X. Wang, J. Li, et al., “Immune Exosomes Loading Self-Assembled Nanomicelles Traverse the Blood-Brain Barrier for Chemo-immunotherapy Against Glioblastoma,” ACS Nano 17, no. 2 (2023): 1464-1484.

[77]

J. Cheng, X. Li, S. Wang, Y. Han, H. Zhao, and X. Yang, “Carrier-Free Triterpene Prodrugs With Glutathione Response and Biosafety for Synergistically Enhanced Photochemotherapy,” ACS Applied Materials & Interfaces 13, no. 1 (2021): 245-256.

[78]

J. Cheng, S. Wang, H. Zhao, Y. Liu, and X. Yang, “Exploring the Self-Assembly Mechanism and Effective Synergistic Antitumor Chemophototherapy of a Biodegradable and Glutathione Responsive Ursolic Acid Prodrug Mediated Photosensitive Nanodrug,” Biomaterials Science 9, no. 10 (2021): 3762-3775.

[79]

R. P. Shukla, P. Tiwari, A. Sardar, et al., “Alendronate-Functionalized Porous Nano-Crystalsomes Mitigate Osteolysis and Consequent Inhibition of Tumor Growth in a Tibia-Induced Metastasis Model,” Journal of Controlled Release 372 (2024): 331-346.

[80]

L. Kang, X. Chang, S. Ma, et al., “Redox-Responsive Self-Assembled HG-type Pectin Nanomicelles for Alleviating Chronic Alcoholic Liver Injury in Mice,” Carbohydrate Polymers 361 (2025): 123619.

[81]

L. Fu, Z. Su, S. Wu, Y. Cheng, C. Hu, and J. Zhang, “Redox-responsive Hyaluronic Acid-Celastrol Prodrug Micelles With Glycyrrhetinic Acid Co-delivery for Tumor Combination Therapy,” Chinese Chemical Letters 36, no. 5 (2025): 110227.

[82]

Y. Zhang, Y. Lian, C. Zhou, et al., “Self-Assembled Natural Triterpenoids for the Delivery of Cyclin-Dependent Kinase 4/6 Inhibitors to Enhance Cancer Chemoimmunotherapy,” Journal of Controlled Release 378 (2025): 791-802.

[83]

X. Zhang, Y. Chen, X. Li, et al., “Carrier-Free Self-Assembled Nanomedicine Based on Celastrol and Galactose for Targeting Therapy of Hepatocellular Carcinoma via Inducing Ferroptosis,” European Journal of Medicinal Chemistry 267 (2024): 116183.

[84]

Z. Li, H. Xie, H. Shi, et al., “Triterpenoids and Ultrasound Dual-Catalytic Nanoreactor Ignites Long-Lived Hypertoxic Reactive Species Storm for Deep Tumor Treatment,” Chemical Engineering Journal 453 (2023): 139938.

[85]

J. Cheng, H. Zhao, B. Li, et al., “Photosensitive Pro-Drug Nanoassemblies Harboring a Chemotherapeutic Dormancy Function Potentiates Cancer Immunotherapy,” Acta Pharmaceutica Sinica B 13, no. 2 (2023): 879-896.

[86]

Z. Li, H. Shi, H. Xie, et al., “Tri-Component Programmable Nanoregulator With Three-Pronged Penetration Boosts Immunotherapy of Triple-Negative Breast Cancer,” Chemical Engineering Journal 439 (2022): 135712.

[87]

Y. Zheng, Z. Li, Y. Yang, H. Shi, H. Chen, and Y. Gao, “A Nanosensitizer Self-Assembled From Oleanolic Acid and Chlorin e6 for Synergistic Chemo/Sono-Photodynamic Cancer Therapy,” Phytomedicine 93 (2021): 153788.

[88]

Y. Bao, S. Zhang, Z. Chen, et al., “Synergistic Chemotherapy for Breast Cancer and Breast Cancer Brain Metastases via Paclitaxel-Loaded Oleanolic Acid Nanoparticles,” Molecular Pharmaceutics 17, no. 4 (2020): 1343-1351.

[89]

S. Fu, M. Wang, B. Li, et al., “Bionic Natural Small Molecule Co-assemblies Towards Targeted and Synergistic Chemo/PDT/CDT,” Biomaterials Research 27, no. 1 (2023): 43.

[90]

J. Wang, W. Qiao, X. Li, et al., “A Directed Co-assembly of Herbal Small Molecules Into Carrier-Free Nanodrugs for Enhanced Synergistic Antitumor Efficacy,” Journal of Materials Chemistry B 9, no. 4 (2021): 1040-1048.

[91]

J. Cheng, H. Zhao, J. Wang, Y. Han, and X. Yang, “Bioactive Natural Small Molecule-Tuned Coassembly of Photosensitive Drugs for Highly Efficient Synergistic and Enhanced Type I Photochemotherapy,” ACS Applied Materials & Interfaces 12, no. 39 (2020): 43488-43500.

[92]

Z. Li, H. Xie, H. Shi, H. Chen, and Y. Gao, “Photosensitizers Dispersed on Nanosized Triterpenoid Matrix With Deaggregation-Enhanced Singlet Oxygen Production,” ACS Applied Materials & Interfaces 15, no. 4 (2023): 4973-4983.

[93]

S. Zhu, Z. Qiu, X. Qiao, et al., “Creating Burdock Polysaccharide-Oleanolic Acid-Ursolic Acid Nanoparticles to Deliver Enhanced Anti-Inflammatory Effects: Fabrication, Structural Characterization and Property Evaluation,” Food Science and Human Wellness 12, no. 2 (2023): 454-466.

[94]

B.-C. Zhang, C.-M. Lai, B.-Y. Luo, and J.-W. Shao, “Triterpenoids-Templated Self-Assembly Nanosystem for Biomimetic Delivery of CRISPR/Cas9 Based on the Synergy of TLR-2 and ICB to Enhance HCC Immunotherapy,” Acta Pharmaceutica Sinica B 14, no. 7 (2024): 3205-3217.

[95]

Z. Wang, J. Liu, Q. Chen, et al., “Bioactive Glycyrrhizic Acid Ionic Liquid Self-Assembled Nanomicelles for Enhanced Transdermal Delivery of Anti-Photoaging Signal Peptides,” Advanced Science 12 (2025): e2412581.

[96]

W. S. Bertaud and R. H. Hedley, “Hexagonal Patterns in Cell Membranes,” Nature 200, no. 4901 (1963): 89-90.

[97]

P. Seeman, D. Cheng, and G. H. Iles, “Structure of Membrane Holes in Osmotic and Saponin Hemolysis,” Journal of Cell Biology 56, no. 2 (1973): 519-527.

[98]

A. Nicol, R. T. K. Kwok, C. Chen, et al., “Ultrafast Delivery of Aggregation-Induced Emission Nanoparticles and Pure Organic Phosphorescent Nanocrystals by Saponin Encapsulation,” Journal of the American Chemical Society 139, no. 41 (2017): 14792-14799.

[99]

A. Weng, M. D. Manunta, M. Thakur, et al., “Improved Intracellular Delivery of Peptide- and Lipid-Nanoplexes by Natural Glycosides,” Journal of Controlled Release 206 (2015): 75-90.

[100]

M. Kolster, A. Sonntag, C. Weise, et al., “Broadening the Scope of Sapofection: Cationic Peptide-Saponin Conjugates Improve Gene Delivery in Vitro and in Vivo,” ACS Applied Materials & Interfaces 16, no. 28 (2024): 36095-36105.

[101]

A. Zarinwall, M. Asadian-Birjand, D. A. Seleci, et al., “Magnetic Nanoparticle-Based Dianthin Targeting for Controlled Drug Release Using the Endosomal Escape Enhancer SO1861,” Nanomaterials 11, no. 4 (2021): 1057.

[102]

I. M. S. Degors, C. Wang, Z. U. Rehman, and I. S. Zuhorn, “Carriers Break Barriers in Drug Delivery: Endocytosis and Endosomal Escape of Gene Delivery Vectors,” Accounts of Chemical Research 52, no. 7 (2019): 1750-1760.

[103]

A. Weng, M. Thakur, B. von Mallinckrodt, et al., “Saponins Modulate the Intracellular Trafficking of Protein Toxins,” Journal of Controlled Release 164, no. 1 (2012): 74-86.

[104]

S. Sama, G. Jerz, P. Schmieder, E. Woith, M. F. Melzig, and A. Weng, “Sapofectosid—Ensuring Non-Toxic and Effective DNA and RNA Delivery,” International Journal of Pharmaceutics 534, no. 1-2 (2017): 195-205.

[105]

J. Clochard, G. Jerz, P. Schmieder, et al., “A New Acetylated Triterpene Saponin From Agrostemma githago L. modulates Gene Delivery Efficiently and Shows a High Cellular Tolerance,” International Journal of Pharmaceutics 589 (2020): 119822.

[106]

I. Welsby, S. Detienne, F. N'Kuli, et al., “Lysosome-Dependent Activation of Human Dendritic Cells by the Vaccine Adjuvant QS-21,” Frontiers in immunology 7 (2016): 663.

[107]

A. Y. Nadeem, A. Shehzad, S. U. Islam, E. A. Al-Suhaimi, and Y. S. Lee, “Mosquirix™ RTS, S/AS01 Vaccine Development, Immunogenicity, and Efficacy,” Vaccines 10, no. 5 (2022): 713.

[108]

M. B. Laurens, “RTS,S/AS01 Vaccine (Mosquirix™): An Overview,” Human Vaccines & Immunotherapeutics 16, no. 3 (2020): 480-489.

[109]

G. E. Hancock, D. J. Speelman, P. J. Frenchick, M. M. Mineo-Kuhn, R. B. Baggs, and D. J. Hahn, “Formulation of the Purified Fusion Protein of respiratory Syncytial Virus With the Saponin QS-21 Induces Protective Immune Responses in Mice That Are Similar to Those Generated by Experimental Infection,” Vaccine 13, no. 4 (1995): 391-400.

[110]

A. D. Robert and A. K. Ruth, “Respiratory Syncytial Virus Vaccines,” Clinical Microbiology Reviews 11, no. 3 (1998): 430-439.

[111]

B. L. Ober Shepherd, P. T. Scott, J. N. Hutter, et al., “SARS-CoV-2 Recombinant Spike Ferritin Nanoparticle Vaccine Adjuvanted With Army Liposome Formulation Containing Monophosphoryl Lipid A and QS-21: A Phase 1, Randomised, Double-Blind, Placebo-Controlled, First-in-Human Clinical Trial,” The Lancet Microbe 5, no. 6 (2024): e581-e593.

[112]

B. S. Ou, J. Baillet, M. V. Filsinger Interrante, et al., “Saponin Nanoparticle Adjuvants Incorporating Toll-Like Receptor Agonists Drive Distinct Immune Signatures and Potent Vaccine Responses,” Science Advances 10, no. 32 (2024): eadn7187.

[113]

C. Wang, Y. Geng, H. Wang, et al., “A Broadly Applicable Protein-Polymer Adjuvant System for Antiviral Vaccines,” EMBO Molecular Medicine 16, no. 6 (2024): 1451-1483.

[114]

L. Derré, V. Cesson, I. Lucca, et al., “Intravesical Bacillus Calmette Guerin Combined With a Cancer Vaccine Increases Local T-Cell Responses in Non-Muscle-Invasive Bladder Cancer Patients,” Clinical Cancer Research 23, no. 3 (2017): 717-725.

[115]

M.-A. Lacaille-Dubois, “Updated Insights Into the Mechanism of Action and Clinical Profile of the Immunoadjuvant QS-21: A Review,” Phytomedicine 60 (2019): 152905.

[116]

P. Yousefpour, Y. J. Zhang, L. Maiorino, et al., “Modulation of Antigen Delivery and Lymph Node Activation in Nonhuman Primates by Saponin Adjuvant Saponin/Monophosphoryl Lipid A Nanoparticle,” PNAS Nexus 3, no. 12 (2024): 529.

[117]

D. J. Marciani, “Vaccine Adjuvants: Role and Mechanisms of Action in Vaccine Immunogenicity,” Drug Discovery Today 8, no. 20 (2003): 934-943.

[118]

D. J. Marciani, “Elucidating the Mechanisms of Action of Saponin-Derived Adjuvants,” Trends in Pharmacological Sciences 39, no. 6 (2018): 573-585.

[119]

C. Pifferi, R. Fuentes, and A. Fernández-Tejada, “Natural and Synthetic Carbohydrate-Based Vaccine Adjuvants and Their Mechanisms of Action,” Nature Reviews Chemistry 5, no. 3 (2021): 197-216.

[120]

S. Zhou, Y. Song, A. Nilam, et al., “The Predominant Quillaja Saponaria Fraction, QS-18, Is Safe and Effective When Formulated in a Liposomal Murine Cancer Peptide Vaccine,” Journal of Controlled Release 369 (2024): 687-695.

[121]

X. Mo, A. Shen, Y. Han, et al., “Polysaccharide Nanoadjuvants Engineered via Phenotype-Specific Nanoprobe-Assisted Phenotypic Screen Reprogram Macrophage Cell Functions for Cancer and Rheumatoid Arthritis Therapy,” ACS Nano 19, no. 13 (2025): 12920-12936.

[122]

C. R. Kensil, U. Patel, M. Lennick, and D. Marciani, “Separation and Characterization of Saponins With Adjuvant Activity From Quillaja saponaria Molina Cortex,” Journal of Immunology 146, no. 2 (1991): 431-437.

[123]

R. Jin, L. Neufeld, and T. L. McGaha, “Linking Macrophage Metabolism to Function in the Tumor Microenvironment,” Nature Cancer 6, no. 2 (2025): 239-252.

[124]

M. H. den Brok, C. Büll, M. Wassink, et al., “Saponin-Based Adjuvants Induce Cross-Presentation in Dendritic Cells by Intracellular Lipid Body Formation,” Nature Communications 7, no. 1 (2016): 13324.

[125]

T. Ichikawa, S. Ishida, Y. Sakiya, Y. Sawada, and M. Hanano, “Biliary Excretion and Enterohepatic Cycling of Glycyrrhizin in Rats,” Journal of Pharmaceutical Sciences 75, no. 7 (1986): 672-675.

[126]

M. Negishi, A. Irie, N. Nagata, and A. Ichikawa, “Specific Binding of Glycyrrhetinic Acid to the Rat Liver Membrane,” Biochimica Et Biophysica Acta 1066, no. 1 (1991): 77-82.

[127]

S. Osaka, H. Tsuji, and H. Kiwada, “Uptake of Liposomes Surface-Modified With Glycyrrhizin by Primary Cultured Rat Hepatocytes,” Biological & Pharmaceutical Bulletin 17, no. 7 (1994): 940-943.

[128]

Y.-Q. Sun, C.-M. Dai, Y. Zheng, S.-D. Shi, H.-Y. Hu, and D.-W. Chen, “Binding Effect of Fluorescence Labeled Glycyrrhetinic Acid With GA Receptors in Hepatocellular Carcinoma Cells,” Life Sciences 188 (2017): 186-191.

[129]

Z. Y. He, X. Zheng, X. H. Wu, et al., “Development of Glycyrrhetinic Acid-Modified Stealth Cationic Liposomes for Gene Delivery,” International Journal of Pharmaceutics 397, no. 1-2 (2010): 147-154.

[130]

L. F. Zhang, W. Q. Deng, Q. W. Huang, et al., “Vicious Cycle-Breaking Lipid Nanoparticles Remodeling Multicellular Crosstalk to Reverse Liver Fibrosis,” Advanced Materials 36, no. 16 (2024): e2311474.

[131]

Y. Wang, W. Wang, H. Yao, et al., “Glycyrrhizic Acid-Based Liposome for Tumor-Targeted Delivery of Cantharidin,” ACS Applied Nano Materials 7, no. 1 (2024): 1030-1044.

[132]

M. Qiu, J. Wang, J. Bai, et al., “Dual-Ligand-Functionalized Liposomes Based on Glycyrrhetinic Acid and cRGD for Hepatocellular Carcinoma Targeting and Therapy,” Molecular Pharmaceutics 20, no. 4 (2023): 1951-1963.

[133]

Q. Tian, C.-N. Zhang, X.-H. Wang, et al., “Glycyrrhetinic Acid-Modified Chitosan/Poly(ethylene glycol) Nanoparticles for Liver-Targeted Delivery,” Biomaterials 31, no. 17 (2010): 4748-4756.

[134]

X. Zhang, X. Xu, X. Wang, et al., “Hepatoma-Targeting and Reactive Oxygen Species-Responsive Chitosan-Based Polymeric Micelles for Delivery of Celastrol,” Carbohydrate Polymers 303 (2023): 120439.

[135]

W. Huang, W. Wang, P. Wang, et al., “Glycyrrhetinic Acid-Modified Poly(ethylene glycol)-b-poly(γ-benzyl l-glutamate) Micelles for Liver Targeting Therapy,” Acta Biomaterialia 6, no. 10 (2010): 3927-3935.

[136]

X. Su, H. Zhong, Y. Zeng, et al., “Dual-Ligand-Functionalized Nanostructured Lipid Carriers as a Novel Dehydrocavidine Delivery System for Liver Fibrosis Therapy,” Colloids and Surfaces B 246 (2025): 114376.

[137]

T. Yan, J. Cheng, Z. Liu, et al., “Acid-Sensitive Polymeric Vector Targeting to Hepatocarcinoma Cells via Glycyrrhetinic Acid Receptor-Mediated Endocytosis,” Materials Science & Engineering, C: Biomimetic and Supramolecular Systems 87 (2018): 32-40.

[138]

W. W. Qi, H. Y. Yu, H. Guo, et al., “Doxorubicin-Loaded Glycyrrhetinic Acid Modified Recombinant human Serum Albumin Nanoparticles for Targeting Liver Tumor Chemotherapy,” Molecular Pharmaceutics 12, no. 3 (2015): 675-683.

[139]

C. Wu, S. Xiang, H. Wang, et al., “Orally Deliverable Sequence-Targeted Fucoxanthin-Loaded Biomimetic Extracellular Vesicles for Alleviation of Nonalcoholic Fatty Liver Disease,” ACS Applied Materials & Interfaces 16, no. 8 (2024): 9854-9867.

[140]

L. Cui, X. Wang, Z. Liu, et al., “Metal-organic Framework Decorated With Glycyrrhetinic Acid Conjugated Chitosan as a pH-Responsive Nanocarrier for Targeted Drug Delivery,” International Journal of Biological Macromolecules 240 (2023): 124370.

[141]

Y. Cai, Y. Xu, H. F. Chan, X. Fang, C. He, and M. Chen, “Glycyrrhetinic Acid Mediated Drug Delivery Carriers for Hepatocellular Carcinoma Therapy,” Molecular Pharmaceutics 13, no. 3 (2016): 699-709.

[142]

L. A. Stecanella, A. P. R. Bitencourt, G. R. Vaz, E. Quarta, J. O. C. Silva Júnior, and A. Rossi, “Glycyrrhizic Acid and Its Hydrolyzed Metabolite 18β-Glycyrrhetinic Acid as Specific Ligands for Targeting Nanosystems in the Treatment of Liver Cancer,” Pharmaceutics 13, no. 11 (2021): 1792.

[143]

A. Speciale, C. Muscarà, M. S. Molonia, M. Cristani, F. Cimino, and A. Saija, “Recent Advances in Glycyrrhetinic Acid-Functionalized Biomaterials for Liver Cancer-Targeting Therapy,” Molecules 27, no. 6 (2022): 1775.

[144]

J. Li, X. Wang, Y. Guo, et al., “Ginsenoside Rg3-engineered Exosomes as Effective Delivery Platform for Potentiated Chemotherapy and Photoimmunotherapy of Glioblastoma,” Chemical Engineering Journal 471 (2023): 144692.

[145]

G. C. Terstappen, A. H. Meyer, R. D. Bell, and W. Zhang, “Strategies for Delivering Therapeutics Across the Blood-Brain Barrier,” Nature Reviews Drug Discovery 20, no. 5 (2021): 362-383.

[146]

I. Zare, S. Zirak Hassan Kiadeh, A. Varol, et al., “Glycosylated Nanoplatforms: From Glycosylation Strategies to Implications and Opportunities for Cancer Theranostics,” Journal of Controlled Release 371 (2024): 158-178.

[147]

L. Zou, Y. Hou, J. Zhang, et al., “Degradable Carrier-Free Spray Hydrogel Based on Self-assembly of Natural Small Molecule for Prevention of Postoperative Adhesion,” Materials Today Bio 22 (2023): 100755.

[148]

H. Yu, G. Zhang, M. You, et al., “Herbal Small Molecule-Based Low/Medium Internal Phase Supramolecular Gel Emulsion for Diabetic Wound Healing,” Journal of Colloid & Interface Science 671 (2024): 270-282.

[149]

T. Li, J. Zheng, M. Xia, et al., “In Situ Sprayed Self-Gelling Powder Self-Assembled by a Pure Molecular Drug From Herbal Extract for Rapid Hemostasis and Neuroprotection in Traumatic Brain Injury,” Advanced Functional Materials 35 (2025): e2419613.

[150]

M. Peng, Q. Peng, W. Li, et al., “Atomic Insights into Self-Assembly of Zingibroside R1 and Its Therapeutic Action against Fungal Diseases,” Advanced Materials (2025): e2503283.

[151]

K. Zhi, Y. Sun, H. Zhao, C. Zhang, H. Peng, and X. Yang, “Self-Assembled Supramolecular Material Derived From Traditional Chinese Medicine: Injectable Self-Assembled Natural Product Gel for Drug Delivery With Biological Activity,” Materials Today Communications 23 (2020): 101149.

[152]

K. Zhi, J. Wang, H. Zhao, and X. Yang, “Self-Assembled Small Molecule Natural Product Gel for Drug Delivery: A Breakthrough in New Application of Small Molecule Natural Products,” Acta Pharmaceutica Sinica B 10, no. 5 (2020): 913-927.

[153]

X. Zhao, M. Liu, Z. Ma, et al., “Constructing a Hydrogel Based on Self-Assembly Properties of Glycyrrhizic Acid: A Drug Delivery System With Digestive Tract Responsive,” Colloids and Surfaces A 697 (2024): 134497.

[154]

W. Liu, Z. Li, Z. Wang, et al., “Functional System Based on Glycyrrhizic Acid Supramolecular Hydrogel: Toward Polymorph Control, Stabilization, and Controlled Release,” ACS Applied Materials & Interfaces 15, no. 6 (2023): 7767-7776.

[155]

J. Zheng, X. Song, Z. Yang, et al., “Self-Assembling Glycyrrhizic Acid Micellar Hydrogels as Encapsulant Carriers for Delivery of Curcumin,” Colloids and Surfaces A 658 (2023): 130680.

[156]

S. K. Panja, S. Patra, and B. G. Bag, “Self-Assembly of the Monohydroxy Triterpenoid Lupeol Yielding Nano-Fibers, Sheets and Gel: Environmental and Drug Delivery Applications,” RSC Advances 11, no. 53 (2021): 33500-33510.

[157]

W. Luo, Z. Yang, J. Zheng, et al., “Small Molecule Hydrogels Loading Small Molecule Drugs From Chinese Medicine for the Enhanced Treatment of Traumatic Brain Injury,” ACS Nano 18, no. 42 (2024): 28894-28909.

[158]

C. Lei, J. Wen, Y. Sun, M. Ren, R. Qiao, and C. Li, “Self-Assembled Herbal Hydrogel for Rectal Administration Therapy in Ulcerative Colitis,” Chemical Engineering Journal 503 (2025): 158477.

[159]

H. Jiang, Q. Lu, X. Huang, et al., “Sinomenine-Glycyrrhizic Acid Self-Assembly Enhanced the Anti-Inflammatory Effect of Sinomenine in the Treatment of Rheumatoid Arthritis,” Journal of Controlled Release 382 (2025): 113718.

[160]

W. Y. He, X. C. Wang, W. Gong, et al., “Construction of an Antibacterial Hydrogel Based on Diammonium Glycyrrhizinate and Gallic Acid for Bacterial-Infected Wound Healing,” Colloids and Surfaces B 222 (2023): 112975.

[161]

Q. Li, Y. Liu, S. Liu, et al., “All-Natural Aggregation-Induced Emission-Active Glycyrrhizic Acid Hydrogels for Drug-Resistant Bacteria-Infected Wound Healing,” Chemical Engineering Journal 512 (2025): 162677.

[162]

D. Song, C. Lu, C. Chang, et al., “Natural Binary Herbal Small Molecules Self-Assembled Nanogel for Synergistic Inhibition of Respiratory Syncytial Virus,” ACS Biomaterials Science & Engineering 10, no. 10 (2024): 6648-6660.

[163]

Y. Yang, D. Cai, Y. Shu, et al., “Natural Small Molecule Self-Assembled Hydrogel Inhibited Tumor Growth and Lung Metastasis of 4T1 Breast Cancer by Regulating the CXCL1/2-S100A8/9 Axis,” Materials and Design 225 (2023): 111435.

[164]

M. Zhan, D. Zhou, L. Lei, et al., “Glycyrrhizic Acid and Glycyrrhetinic Acid Loaded Cyclodextrin MOFs With Enhanced Antibacterial and Anti-Inflammatory Effects for Accelerating Diabetic Wound Healing,” Colloids and Surfaces B 245 (2025): 114200.

[165]

X. Fu, Y. Ni, G. Wang, et al., “Synergistic and Long-Lasting Wound Dressings Promote Multidrug-Resistant Staphylococcus Aureus-Infected Wound Healing,” International Journal of Nanomedicine 18 (2023): 4663-4679.

[166]

C. Zhang, S. Sun, T. Zhu, et al., “NIR-Activating Glycyrrhizic Acid/Carbon Nanozyme Injectable Polysaccharides-Based Hydrogels for Promoting Polymicrobial Infected Wound Healing,” International Journal of Biological Macromolecules 307 (2025): 142082.

[167]

Y. Hou, M. Chen, H. Ruan, et al., “A New Supramolecular Natural Product Gel Based on Self-Assembled Pomolic Acid From Traditional Chinese Medicine,” Colloid and Interface Science Communications 46 (2022): 100583.

[168]

B. G. Bag and S. S. Dash, “First Self-Assembly Study of Betulinic Acid, a Renewable Nano-Sized, 6-6-6-6-5 Pentacyclic Monohydroxy Triterpenic Acid,” Nanoscale 3, no. 11 (2011): 4564.

[169]

D. Cai, Y. Yang, J. Lu, et al., “Injectable Carrier-Free Hydrogel Dressing With Anti-Multidrug-Resistant Staphylococcus aureus and Anti-Inflammatory Capabilities for Accelerated Wound Healing,” ACS Applied Materials & Interfaces 14, no. 38 (2022): 43035-43049.

[170]

Y. Gao, J. Hao, J. Wu, X. Zhang, J. Hu, and Y. Ju, “Supramolecular Helical Nanofibers Assembled From a Pyridinium-Functionalized Methyl Glycyrrhetate Amphiphile,” Nanoscale 7, no. 32 (2015): 13568-13575.

[171]

Q. Li, S. Zhang, R. Du, et al., “Injectable Self-Healing Adhesive Natural Glycyrrhizic Acid Bioactive Hydrogel for Bacteria-Infected Wound Healing,” ACS Applied Materials & Interfaces 15, no. 14 (2023): 17562-17576.

[172]

J.-P. Fan, F.-H. Tao, X.-H. Zhang, et al., “Synthesis of an Ursolic Acid Organic Salt Based Low-Molecular-Weight Supramolecular Hydrogel With Unique Thermo-Responsiveness Behavior,” Colloids and Surfaces A 652 (2022): 129839.

[173]

S. Guo, S. Chen, N. Cao, et al., “A Novel 18β-Glycyrrhetinic Acid Derivative Supramolecular Self-Assembly Hydrogel With Antibacterial Activity,” Journal of Materials Science 56, no. 30 (2021): 17254-17267.

[174]

J.-P. Fan, H. Zhong, X.-H. Zhang, T.-T. Yuan, H.-P. Chen, and H.-L. Peng, “Preparation and Characterization of Oleanolic Acid-Based Low-Molecular-Weight Supramolecular Hydrogels Induced by Heating,” ACS Applied Materials & Interfaces 13, no. 24 (2021): 29130-29136.

[175]

Z. Özdemir, D. Šaman, K. Bertula, et al., “Rapid Self-Healing and Thixotropic Organogelation of Amphiphilic Oleanolic Acid-Spermine Conjugates,” Langmuir 37, no. 8 (2021): 2693-2706.

[176]

L. Zhao, H. Zhang, Z. Guo, et al., “Natural Glycyrrhizic Acid-Tailored Homogeneous Conductive Polyaniline Hydrogel as a Flexible Strain Sensor,” ACS Applied Materials & Interfaces 14, no. 45 (2022): 51394-51403.

[177]

L. Zou, Y. Hou, X. Nie, et al., “All-Small-Molecule Supramolecular Hydrogel Combining Self-Delivery and ROS-Responsive Release for Inhibiting Tumor Growth and Postoperative Recurrence,” ACS Applied Materials & Interfaces 17, no. 9 (2025): 13494-13512.

[178]

Y. Gao, K. Zhao, X. Yu, et al., “Multiple Modulations of Supramolecular Assemblies From a Natural Triterpenoid-Tailored Bipyridinium Amphiphile,” Journal of Colloid & Interface Science 584 (2021): 92-102.

[179]

X. Yu, M. Xu, J. Cai, et al., “Tunable Glycyrrhizic Acid Supramolecular Hydrogels via Metal Ion Complexation,” Giant 17 (2024): 100240.

[180]

X. Yu, J. Cai, M. Xu, et al., “A Natural Food-Grade Supramolecular Self-Assembly System for Creation of Hierarchically Structured Hydrogels,” Nanoscale 16, no. 30 (2024): 14261-14268.

[181]

Z. Wang, J. Liu, Y. Zheng, et al., “Copper Ion-Inspired Dual Controllable Drug Release Hydrogels for Wound Management: Driven by Hydrogen Bonds,” Small 20, no. 34 (2024): e2401152.

[182]

F. Zhang, C. Yin, X. Qi, C. Guo, and X. Wu, “Silk Fibroin Crosslinked Glycyrrhizic Acid and Silver Hydrogels for Accelerated Bacteria-Infected Wound Healing,” Macromolecular Bioscience 22, no. 4 (2022): 2100407.

[183]

X. Li, Y. Li, A. Tehoungue, et al., “An Antibacterial Hydrogel Based on Silk Sericin Cross-Linking Glycyrrhizic Acid and Silver for Infectious Wound Healing,” Biomacromolecules 26, no. 4 (2025): 2356-2367.

[184]

X. Zhang, L. Yang, W. Pi, et al., “Natural Diterpene Carrier-Free Hydrogel Enhances Antigen Presentation and Intensifies T Cell Activation for Tumor Immunotherapy,” Chemical Engineering Journal 500 (2024): 156383.

[185]

Y. Fu, H. Sun, Y. Jin, et al., “Self-Assembled Antioxidant Enzyme-Mimicking Hydrogel: Targeting Oxidative Stress and Macrophage Organization for Improving Degenerated Intervertebral Discs,” Materials Today Bio 31 (2025): 101586.

[186]

W. Zhang, S. Zhao, H. Zhang, et al., “A Simple and Universal Approach for Fabricating Bioactive Self-Stacked Hydrogels With Enhanced Therapeutic Efficacy,” Chemical Engineering Journal 496 (2024): 154316.

[187]

W. Zhang, S. Zhao, Q. Guan, P. Li, and Y. Fan, “Enhancing Chronic Wound Healing Through Engineering Mg 2+ -Coordinated Asiatic Acid/Bacterial Cellulose Hybrid Hydrogels,” ACS Applied Materials & Interfaces 16, no. 7 (2024): 8238-8249.

[188]

Y. Qian, Y. Zheng, J. Jin, et al., “Immunoregulation in Diabetic Wound Repair With a Photoenhanced Glycyrrhizic Acid Hydrogel Scaffold,” Advanced Materials 34, no. 29 (2022): e2200521.

[189]

C. Lu, C. Chang, Y. Zheng, et al., “Supramolecular Self-Assembled Hydrogel for Antiviral Therapy Through Glycyrrhizic Acid-Enhanced Zinc Absorption and Intracellular Accumulation,” ACS Applied Materials & Interfaces 16, no. 44 (2024): 60027-60044.

[190]

J. Li, D. Wu, Z. Su, et al., “Zinc-Induced Photocrosslinked Konjac Glucomannan/Glycyrrhizic Acid Hydrogel Promotes Skin Wound Healing in Diabetic Mice Through Immune Regulation,” Carbohydrate Polymers 348 (2025): 122780.

[191]

J. Wang, W. Wang, K. Li, et al., “A Functional Hydrogel Dressing Based on Glycyrrhizic Acid With Low-Swelling and Moisturizing Properties for Enhancing Infected Wound Repair,” Journal of Materials Chemistry B 13, no. 2 (2025): 656-667.

[192]

R. Huang, C. Hu, S. Xu, et al., “3D-Printed Bifunctional Scaffold for Treatment of Critical Bone Defects Based on Osteoimmune Microenvironment Regulation and Osteogenetic Effects,” ACS Applied Materials & Interfaces 16, no. 46 (2024): 63345-63357.

[193]

L. Wu, W. Pi, X. Huang, et al., “Orchestrated Metal-Coordinated Carrier-Free Celastrol Hydrogel Intensifies T Cell Activation and Regulates Response to Immune Checkpoint Blockade for Synergistic Chemo-Immunotherapy,” Biomaterials 312 (2025): 122723.

[194]

W. Pi, L. Wu, J. Lu, et al., “A Metal Ions-Mediated Natural Small Molecules Carrier-Free Injectable Hydrogel Achieving Laser-Mediated Photo-Fenton-Like Anticancer Therapy by Synergy Apoptosis/Cuproptosis/Anti-Inflammation,” Bioactive Materials 29 (2023): 98-115.

[195]

X. Jia, Y. Dong, J. Lu, et al., “A Self-Assembly Enzyme-Like Hydrogel With ROS Scavenging and Immunomodulatory Capability for Microenvironment-Responsive Wound Healing Acceleration,” International Journal of Pharmaceutics 675 (2025): 125529.

[196]

Z. Xu, Z. Xu, J. Gu, et al., “In Situ Formation of Ferrous Sulfide in Glycyrrhizic Acid Hydrogels to Promote Healing of Multi-Drug Resistant Staphylococcus aureus-Infected Diabetic Wounds,” Journal of Colloid & Interface Science 650, no. Pt B (2023): 1918-1929.

[197]

Z. Xu, Z. Gao, J. Lu, et al., “Ferrous Iron-Induced Formation of Glycyrrhizic Acid Hydrogels for Staphylococcus aureus-Infected Wound Healing,” Colloids and Surfaces B 221 (2023): 112977.

[198]

Y. Wu, Z. Gu, T. Chen, et al., “Effect of Different Crosslinking Agents on Carboxymethyl Chitosan-Glycyrrhizic Acid Hydrogel: Characterization and Biological Activities Comparison,” International Journal of Biological Macromolecules 298 (2025): 139977.

[199]

C. Lu, Q. Sun, Z. Li, et al., “Injectable Glycyrrhizinate-Pectin Hydrogel Wound Dressing Based on Natural Ingredients,” Carbohydrate Polymers 359 (2025): 123562.

[200]

C. Zhang, E. Cai, X. Qi, et al., “Immunomodulatory Gallium/Glycyrrhizic Acid Hydrogels for Treating Multidrug-Resistant Pseudomonas Aeruginosa-Infected Pressure Ulcers,” Chemical Engineering Journal 487 (2024): 150756.

[201]

X. Qi, Y. Shi, C. Zhang, et al., “A Hybrid Hydrogel With Intrinsic Immunomodulatory Functionality for Treating Multidrug-Resistant Pseudomonas aeruginosa Infected Diabetic Foot Ulcers,” ACS Materials Letters 6, no. 7 (2024): 2533-2547.

[202]

B. Dalisson and J. Barralet, “Bioinorganics and Wound Healing,” Advanced Healthcare Materials 8, no. 18 (2019): e1900764.

[203]

P. Bonaventura, G. Benedetti, F. Albarède, and P. Miossec, “Zinc and Its Role in Immunity and Inflammation,” Autoimmunity Reviews 14, no. 4 (2015): 277-285.

[204]

Y. Yuan, H. Zhao, X. Yin, D. Wang, X. Mei, and P. Zhang, “Alloy Nanozyme-Reinforced Hyaluronic Acid-Based Hydrogel With Wound Environment-Responsive Properties for Synergistically Accelerating Infectious Wound Healing,” International Journal of Biological Macromolecules 269 (2024): 131896.

[205]

M. Saeedi, M. R. Moghbeli, and O. Vahidi, “Chitosan/Glycyrrhizic Acid Hydrogel: Preparation, Characterization, and Its Potential for Controlled Release of Gallic Acid,” International Journal of Biological Macromolecules 231 (2023): 123197.

[206]

H. Zhang, N. Tang, X. Yu, et al., “Natural Glycyrrhizic Acid-Tailored Hydrogel With In-Situ Gradient Reduction of AgNPs Layer as High-Performance, Multi-Functional, Sustainable Flexible Sensors,” Chemical Engineering Journal 430 (2022): 132779.

[207]

Z. Zheng, Z. Wu, C. Li, et al., “Enhanced Immunoregulation in Traumatic Urethral Stricture Repair Utilizing a Glycyrrhizic Acid-Infused Antiswelling Biogel Scaffold,” RSC Advances 15, no. 18 (2025): 14217-14226.

[208]

B. Zhang, W. Wang, P. Gao, et al., “Injectable, Electroconductive, Free Radical Scavenging Silk Fibroin/Black Phosphorus/Glycyrrhizic Acid Nanocomposite Hydrogel for Enhancing Spinal Cord Repair,” Advanced Healthcare Materials 13, no. 18 (2024): e2304300.

[209]

H. Wu, Z. Xue, Z. Wang, et al., “Injectable Glycyrrhizic Acid-Based Hydrogel With Immunoregulatory and Angiogenic Properties for Diabetic Wound Healing,” Materials and Design 253 (2025): 113928.

[210]

X. F. Tong, F. Q. Zhao, Y. Z. Ren, Y. Zhang, Y. L. Cui, and Q. S. Wang, “Injectable Hydrogels Based on Glycyrrhizin, Alginate, and Calcium for Three-Dimensional Cell Culture in Liver Tissue Engineering,” Journal of Biomedical Materials Research, Part A 106, no. 12 (2018): 3292-3302.

[211]

J. Ge, C. Fang, H. Tan, et al., “Endogenous Zinc-Ion-Triggered in Situ Gelation Enables Zn Capture to Reprogram Benign Hyperplastic Prostate Microenvironment and Shrink Prostate,” Advanced Materials 36, no. 11 (2024): e2307796.

[212]

Q. Li, X. Yu, S. Zhang, et al., “All-Natural, Robust, and pH-Responsive Glycyrrhizic Acid-Based Double Network Hydrogels for Controlled Nutrient Release,” ACS Appl Mater Interfaces 15, no. 37 (2023): 43633-43647.

[213]

F.-Q. Zhao, G.-F. Wang, D. Xu, H.-Y. Zhang, Y.-L. Cui, and Q.-S. Wang, “Glycyrrhizin Mediated Liver-Targeted Alginate Nanogels Delivers Quercetin to Relieve Acute Liver Failure,” International Journal of Biological Macromolecules 168 (2021): 93-104.

[214]

J. Sun, M. Sun, J. Zang, T. Zhang, C. Lv, and G. Zhao, “Highly Stretchable, Transparent, and Adhesive Double-Network Hydrogel Dressings Tailored With Fish Gelatin and Glycyrrhizic Acid for Wound Healing,” ACS Applied Materials & Interfaces 15, no. 36 (2023): 42304-42316.

[215]

L. Tan, S. Wu, L. Liu, et al., “Bacterial Cellulose Based Gel of Glycyrrhizic Acid Gel for Atopic Dermatitis: Design, Optimization, in Vitro and in Vivo Investigation,” International Journal of Biological Macromolecules 286 (2025): 138425.

[216]

S. Qin, H. Li, X. Liu, et al., “Supramolecular Nanofiber Network Hydrogel Dressing for Promoting Wound Healing With Low Swelling and Mechanical Stability Properties,” Colloids and Surfaces B 245 (2025): 114345.

[217]

W.-J. Yin, X.-W. Chen, C.-G. Ma, and J.-M. Wang, “Fabrication and Characterization of Tunable High Internal Phase Emulsion Gels (HIPE-Gels) Formed by Natural Triterpenoid Saponin and Plant Soy Protein,” ACS Food Science & Technology 2, no. 7 (2022): 1103-1113.

[218]

Q. Cui, X. Song, L. Zhou, et al., “Fabrication of Resveratrol-Loaded Soy Protein Isolate-Glycyrrhizin Nanocomplex for Improving Bioavailability via pH-Responsive Hydrogel Properties,” International Journal of Biological Macromolecules 258 (2024): 128950.

[219]

Z. Cui, X. Zhang, L. Zhou, et al., “A Carrier-Free Injectable Hydrogel Self-Assembled Using Natural Thymol and Glycyrrhizin for MRSA-Infected Wound Healing in Rats,” Chemical Engineering Journal 489 (2024): 151418.

[220]

H. Zheng, S. Gao, Y. Liu, et al., “Bioactive Glycyrrhizic Acid-Astragalus Polysaccharide Hydrogel Facilitates Gastric Ulcer Healing via ROS Scavenging and Anti-Apoptotic Effects,” Carbohydrate Polymers 362 (2025): 123685.

[221]

H. Sun, Z. Dong, X. Kou, et al., “Herbal Molecule-Mediated Dual Network Hydrogels With Adhesive and Antibacterial Properties for Strain and Pressure Sensing,” RSC Advances 13, no. 9 (2023): 5762-5769.

[222]

D. Y. Zhu, Z. P. Chen, Z. P. Hong, et al., “Injectable Thermo-Sensitive and Wide-Crack Self-Healing Hydrogel Loaded With Antibacterial Anti-Inflammatory Dipotassium Glycyrrhizate for Full-Thickness Skin Wound Repair,” Acta Biomaterialia 143 (2022): 203-215.

[223]

X. Liu, X. Cheng, Y. Sun, et al., “Peptide/Glycyrrhizic Acid Supramolecular Polymer: An Emerging Medical Adhesive for Dural Sealing and Repairing,” Biomaterials 301 (2023): 122239.

[224]

L. Zhang, Z. Luo, H. Chen, X. Wu, and Y. Zhao, “Glycyrrhizic Acid Hydrogel Microparticles Encapsulated With Mesenchymal Stem Cell Exosomes for Wound Healing,” Research 7 (2024): 0496.

[225]

X. Li, L. Guan, X. Li, et al., “A Hierarchical Hydrogel Dressing With Continuous Biochemical Gradient for Immunoregulation, Nerve Repair and Angiogenesis of Refractory Diabetes Wounds,” Chinese Chemical Letters (2024): 110661.

[226]

Q. Guo, R. Li, Y. Zhao, et al., “An Injectable, Self-Healing, Anti-Infective, and Anti-Inflammatory Novel Glycyrrhizic Acid Hydrogel for Promoting Acute Wound Healing and Regeneration,” Frontiers in Bioengineering and Biotechnology 12 (2025): 1525644.

[227]

Y. Fan, Z. Niu, L. Yin, et al., “Membrane Biomimetic Nanoenzyme-Incorporated Hybrid Glycyrrhizic Acid Hydrogel for Precise Mitochondrial ROS Scavenging for Osteoarthritis Treatment,” Materials Today Bio 32 (2025): 101778.

[228]

X. Wang, H. Huo, Y. Zhong, et al., “Synergistic Antimicrobial Glycyrrhizic Acid-Based Functional Biosensing Composite for Sensitive Glucose Monitoring and Collaborative Wound Healing,” Advanced Healthcare Materials 13, no. 20 (2024): e2400580.

[229]

S. Bao, A. Jiang, L. Peng, et al., “Injectable Dual-Network Hydrogel for Phototherapy and Immunomodulation in the Treatment of MRSA-Infected and Diabetic Wound,” Chemical Engineering Journal 513 (2025): 163026.

[230]

Y. Zheng, L. Fu, Z. Zhang, et al., “Three-Dimensional Bioprinting of Growth Differentiation Factor 5-Preconditioned Mesenchymal Stem Cell-Derived Exosomes Facilitates Articular Cartilage Endogenous Regeneration,” ACS Nano 19, no. 16 (2025): 15281-15301.

[231]

Y. Ji, Y. Yuan, F. Peng, et al., “Two-Component Hydrogels Built From Chinese Herbal Medicine-Derived Glycyrrhizic Acid and Puerarin: Assembly Mechanism, Self-Healing Properties, and Selective Antibacterial Activity,” ACS Applied Materials & Interfaces 17, no. 3 (2025): 5223-5231.

[232]

R. Mathiyalagan, M. Murugesan, Z. M. Ramadhania, et al., “Triterpenoid Saponin-Based Supramolecular Host-Guest Injectable Hydrogels Inhibit the Growth of Melanoma via ROS-Mediated Apoptosis,” Materials Science and Engineering R: Reports 160 (2024): 100824.

[233]

H. Huang, X. Yang, X. Qin, et al., “Co-Assembled Supramolecular Hydrogel of Asiaticoside and Panax Notoginseng Saponins for Enhanced Wound Healing,” European Journal of Pharmaceutics and Biopharmaceutics 207 (2025): 114617.

[234]

F. Topuz and T. Uyar, “Advances in the Development of Cyclodextrin-Based Nanogels/Microgels for Biomedical Applications: Drug Delivery and Beyond,” Carbohydrate Polymers 297 (2022): 120033.

[235]

Y. Li, J. Li, X. Zhao, et al., “Triterpenoid-Based Self-Healing Supramolecular Polymer Hydrogels Formed by Host-Guest Interactions,” Chemistry— A European Journal 22, no. 51 (2016): 18435-18441.

[236]

G. Xu, J. Li, J. Wu, H. Zhang, J. Hu, and M.-H. Li, “Tough Polymeric Hydrogels Formed by Natural Glycyrrhetinic Acid-Tailored Host-Guest Macro-Cross-Linking Toward Biocompatible Materials,” ACS Applied Polymer Materials 1, no. 10 (2019): 2577-2581.

[237]

J. Hao, Y. Gao, Y. Li, Q. Yan, J. Hu, and Y. Ju, “Thermosensitive Triterpenoid-Appended Polymers With Broad Temperature Tunability Regulated by Host-Guest Chemistry,” Chemistry Asian Journal 12, no. 17 (2017): 2231-2236.

[238]

Y. Zhang, F. Li, G. Guo, et al., “Preparation and Characterization of Betulin/Methyl-Beta-Cyclodextrin Inclusion Complex Electrospun Nanofiber: Improving the Properties of Betulin,” Industrial Crops and Products 209 (2024): 117974.

[239]

M. Li, S. Wang, Y. Li, et al., “An Integrated All-Natural Conductive Supramolecular Hydrogel Wearable Biosensor With Enhanced Biocompatibility and Antibacterial Properties,” ACS Applied Materials & Interfaces 16, no. 38 (2024): 51618-51629.

[240]

J. Zheng, R. Fan, H. Wu, et al., “Directed Self-Assembly of Herbal Small Molecules Into Sustained Release Hydrogels for Treating Neural Inflammation,” Nature Communications 10, no. 1 (2019): 1604.

[241]

Y. Cai, J. Zhang, Y. He, et al., “A Supramolecular Hydrogel of Puerarin,” Journal of Biomedical Nanotechnology 14, no. 2 (2018): 257-266.

[242]

K. J. De France, F. Xu, and T. Hoare, “Structured Macroporous Hydrogels: Progress, Challenges, and Opportunities,” Advanced Healthcare Materials 7 (2018): e1700927.

[243]

D. Zhao, L. Qian, Q. Yang, et al., “Microfluidic Synthesis of Stimuli-Responsive Hydrogel Particles,” Applied Materials Today 42 (2025): 102571.

[244]

L. Li, J. M. Scheiger, and P. A. Levkin, “Design and Applications of Photoresponsive Hydrogels,” Advanced Materials 31, no. 26 (2019): e1807333.

[245]

A. P. Dhand, M. D. Davidson, and J. A. Burdick, “Lithography-Based 3D Printing of Hydrogels,” Nature Reviews Bioengineering 3, no. 2 (2025): 108-125.

[246]

M. Zhang, S. Xu, R. Wang, et al., “Electrospun Nanofiber/Hydrogel Composite Materials and Their Tissue Engineering Applications,” Journal of Materials Science and Technology 162 (2023): 157-178.

[247]

G. Guerrini, D. Magrì, S. Gioria, D. Medaglini, and L. Calzolai, “Characterization of Nanoparticles-Based Vaccines for COVID-19,” Nature Nanotechnology 17, no. 6 (2022): 570-576.

[248]

R. Tenchov, R. Bird, A. E. Curtze, and Q. Zhou, “Lipid Nanoparticles─From Liposomes to mRNA Vaccine Delivery, a Landscape of Research Diversity and Advancement,” ACS Nano 15, no. 11 (2021): 16982-17015.

[249]

T. M. Allen and P. R. Cullis, “Liposomal Drug Delivery Systems: From Concept to Clinical Applications,” Advanced Drug Delivery Reviews 65, no. 1 (2013): 36-48.

[250]

W. W. Sułkowski, D. Pentak, K. Nowak, and A. Sułkowska, “The Influence of Temperature, Cholesterol Content and pH on Liposome Stability,” Journal of Molecular Structure 744-747 (2005): 737-747.

[251]

S. Kaddah, N. Khreich, F. Kaddah, and C. Charcosset, “Cholesterol Modulates the Liposome Membrane Fluidity and Permeability for a Hydrophilic Molecule,” Food and Chemical Toxicology 113 (2018): 40-48.

[252]

M.-L. Briuglia, C. Rotella, A. McFarlane, and D. A. Lamprou, “Influence of Cholesterol on Liposome Stability and on in Vitro Drug Release,” Drug Delivery and Translational Research 5, no. 3 (2015): 231-242.

[253]

P. I. Back, M. Yu, S. Modaresahmadi, et al., “Immune Implications of Cholesterol-Containing Lipid Nanoparticles,” ACS Nano 18, no. 42 (2024): 28480-28501.

[254]

A. Kloudova, F. P. Guengerich, and P. Soucek, “The Role of Oxysterols in Human Cancer,” Trends in Endocrinology and Metabolism 28, no. 7 (2017): 485-496.

[255]

X. Ma, E. Bi, Y. Lu, et al., “Cholesterol Induces CD8+ T Cell Exhaustion in the Tumor Microenvironment,” Cell Metabolism 30, no. 1 (2019): 143-156.e145.

[256]

G. M. Swartz, M. K. Gentry, L. M. Amende, E. J. Blanchette-Mackie, and C. R. Alving, “Antibodies to Cholesterol,” Proceedings National Academy of Science USA 85, no. 6 (1988): 1902-1906.

[257]

S. Moein Moghimi, I. Hamad, R. Bünger, et al., “Activation of the Human Complement System by Cholesterol-Rich and PEGylated Liposomes—Modulation of Cholesterol-Rich Liposome-Mediated Complement Activation by Elevated Serum LDL and HDL Levels,” Journal of Liposome Research 16, no. 3 (2006): 167-174.

[258]

J. Szebeni, L. Baranyi, S. Savay, et al., “Liposome-Induced Pulmonary Hypertension: Properties and Mechanism of a Complement-Mediated Pseudoallergic Reaction,” American Journal of Physiology 279, no. 3 (2000): H1319-H1328.

[259]

F. Zahednezhad, M. Saadat, H. Valizadeh, P. Zakeri-Milani, and B. Baradaran, “Liposome and Immune System Interplay: Challenges and Potentials,” Journal of Controlled Release 305 (2019): 194-209.

[260]

Q. Yang, P. Guo, P. Lei, et al., “Dissolvable Microneedles Loaded Ginsenoside Rg3 Liposome: A Transdermal Delivery Approach for Alopecia Treatment,” Regenerative Biomaterials 11 (2024): rbae086.

[261]

X. Zhang, S. Li, Y. Dong, H. Rong, J. Zhao, and H. Hu, “A Multifunctional Cholesterol-Free Liposomal Platform Based on Protopanaxadiol for Alopecia Therapy,” Nano Research 15, no. 10 (2022): 9498-9510.

[262]

Y. Eygeris, S. Patel, A. Jozic, and G. Sahay, “Deconvoluting Lipid Nanoparticle Structure for Messenger RNA Delivery,” Nano Letters 20, no. 6 (2020): 4543-4549.

[263]

K. Tai, M. Rappolt, X. He, et al., “Effect of β-Sitosterol on the Curcumin-Loaded Liposomes: Vesicle Characteristics, Physicochemical Stability, in Vitro Release and Bioavailability,” Food Chemistry 293 (2019): 92-102.

[264]

A. A. Jovanović, B. D. Balanč, A. Ota, et al., “Comparative Effects of Cholesterol and β-Sitosterol on the Liposome Membrane Characteristics,” European Journal of Lipid Science and Technology 120, no. 9 (2018): 1800039.

[265]

M. Cui, W. Wu, L. Hovgaard, Y. Lu, D. Chen, and J. Qi, “Liposomes Containing Cholesterol Analogues of Botanical Origin as Drug Delivery Systems to Enhance the Oral Absorption of Insulin,” International Journal of Pharmaceutics 489, no. 1 (2015): 277-284.

[266]

C. Zhong, T. Liu, J. Diao, X. Li, M. Liu, and Y. Wang, “Preparation and Characterization of Astaxanthin-Loaded Liposomes by Phytosterol Oleate Instead of Cholesterol,” Food Chemistry 462 (2025): 141008.

[267]

S. Patel, N. Ashwanikumar, E. Robinson, et al., “Naturally-Occurring Cholesterol Analogues in Lipid Nanoparticles Induce Polymorphic Shape and Enhance Intracellular Delivery of mRNA,” Nature Communications 11, no. 1 (2020): 983.

[268]

X. Xiao, X. Wu, Z. Yu, and J. He, “Incorporation of the Sterol From Camellia Oil Deodorant Distillate Into Vitamin C Liposomes: Vesicle Characteristics, Stability, Release, and Bioavailability,” Food Biophysics 18, no. 1 (2023): 10-22.

[269]

G. Liu, P. Sun, J. Yan, P. Shao, and S. Feng, “Regulation of Nanoliposome Rigidity and Bioavailability of Oligomeric Proanthocyanidin With Phytosterols Containing Different C3 Branches,” ACS Applied Materials & Interfaces 15, no. 37 (2023): 43414-43430.

[270]

S. K. Patel, M. M. Billingsley, A. J. Mukalel, et al., “Bile Acid-Containing Lipid Nanoparticles Enhance Extrahepatic mRNA Delivery,” Theranostics 14, no. 1 (2024): 1-16.

[271]

M. Jiang, L. Chen, C. Hong, et al., “A Novel Polyphyllin I-Based Liposome Delivery System Sensitizes Hepatic Carcinoma to Doxorubicin via Cholesterol Modulation,” Journal of Drug Delivery Science and Technology 78 (2022): 103925.

[272]

L. Chen, J. Lan, Z. Li, et al., “A Novel Diosgenin-Based Liposome Delivery System Combined With Doxorubicin for Liver Cancer Therapy,” Pharmaceutics 14, no. 8 (2022): 1685.

[273]

G. Liu, J. Liu, P. Shao, et al., “Novel Nanoliposomes Synergistically Modulated by Sitogluside and Dioscin: Stability, Bioavailability, and Capacity To Alleviate Hyperuricaemia,” Journal of Agricultural and Food Chemistry 73, no. 4 (2025): 2596-2612.

[274]

M. Z. Wang, Y. Xu, J. F. Xie, Z. H. Jiang, and L. H. Peng, “Ginsenoside as a New Stabilizer Enhances the Transfection Efficiency and Biocompatibility of Cationic Liposome,” Biomaterials Science 9, no. 24 (2021): 8373-8385.

[275]

X. Li, A. S. Widjaya, J. Liu, X. Liu, Z. Long, and Y. Jiang, “Cell-Penetrating Corosolic Acid Liposome as a Functional Carrier for Delivering Chemotherapeutic Drugs,” Acta Biomaterialia 106 (2020): 301-313.

[276]

A. S. Widjaya, Y. Liu, Y. Yang, W. Yin, J. Liang, and Y. Jiang, “Tumor-Permeable Smart Liposomes by Modulating the Tumor Microenvironment to Improve the Chemotherapy,” Journal of Controlled Release 344 (2022): 62-79.

[277]

R. Li, L. Y. Zhang, Z. J. Li, et al., “Characterization and Absorption Kinetics of a Novel Multifunctional Nanoliposome Stabilized by Sea Cucumber Saponins Instead of Cholesterol,” Journal of Agricultural and Food Chemistry 68, no. 2 (2020): 642-651.

[278]

J. Xia, C. Chen, M. Dong, et al., “Ginsenoside Rg3 Endows Liposomes With Prolonged Blood Circulation and Reduced Accelerated Blood Clearance,” Journal of Controlled Release 364 (2023): 23-36.

[279]

J. Zhou, B. Gao, H. Zhang, et al., “Ginsenoside Modified Lipid-Coated Perfluorocarbon Nanodroplets: A Novel Approach to Reduce Complement Protein Adsorption and Prolong in Vivo Circulation,” Acta Pharmaceutica Sinica B 14, no. 4 (2024): 1845-1863.

[280]

C. Hong, D. Wang, J. Liang, et al., “Novel Ginsenoside-Based Multifunctional Liposomal Delivery System for Combination Therapy of Gastric Cancer,” Theranostics 9, no. 15 (2019): 4437-4449.

[281]

X. Wang, W. Zheng, Q. Shen, et al., “Identification and Construction of a Novel Biomimetic Delivery System of paclitaxel and Its Targeting Therapy for Cancer,” Signal Transduction and Targeted Therapy 6, no. 1 (2021): 33.

[282]

Y. Zhang, Y. Wang, H. Zhang, et al., “Replacing Cholesterol With Asiatic Acid to Prolong Circulation and Enhance Anti-Metastatic Effects of Non-PEGylated Liposomes,” Journal of Controlled Release 366 (2024): 585-595.

[283]

T. Van de Vyver, B. Bogaert, L. De Backer, et al., “Cationic Amphiphilic Drugs Boost the Lysosomal Escape of Small Nucleic Acid Therapeutics in a Nanocarrier-Dependent Manner,” ACS Nano 14, no. 4 (2020): 4774-4791.

[284]

C. Muntean, E. Blondeel, L. Harinck, et al., “Repositioning the Antihistamine Ebastine as an Intracellular siRNA Delivery Enhancer,” International Journal of Pharmaceutics 644 (2023): 123348.

[285]

B. Bogaert, A. Debisschop, T. Ehouarne, et al., “Selective Replacement of Cholesterol With Cationic Amphiphilic Drugs Enables the Design of Lipid Nanoparticles With Improved RNA Delivery,” Nano Letters 24, no. 10 (2024): 2961-2971.

[286]

C. Hong, J. Liang, J. Xia, et al., “One Stone Four Birds: A Novel Liposomal Delivery System Multi-Functionalized With Ginsenoside Rh2 for Tumor Targeting Therapy,” Nanomicro Letters 12, no. 1 (2020): 129.

[287]

J. Lan, L. Chen, Z. Li, et al., “Multifunctional Biomimetic Liposomes With Improved Tumor-Targeting for TNBC Treatment by Combination of Chemotherapy, Antiangiogenesis and Immunotherapy,” Advanced Healthcare Materials 13 (2024): e2400046.

[288]

J. Xia, S. Ma, X. Zhu, et al., “Versatile Ginsenoside Rg3 Liposomes Inhibit Tumor Metastasis by Capturing Circulating Tumor Cells and Destroying Metastatic Niches,” Science Advances 8, no. 6 (2022): eabj1262.

[289]

Y. Zhu, J. Liang, C. Gao, et al., “Multifunctional Ginsenoside Rg3-Based Liposomes for Glioma Targeting Therapy,” Journal of Controlled Release 330 (2021): 641-657.

[290]

Y. Zhu, A. Wang, S. Zhang, et al., “Paclitaxel-loaded Ginsenoside Rg3 Liposomes for Drug-Resistant Cancer Therapy by Dual Targeting of the Tumor Microenvironment and Cancer Cells,” Journal of Advanced Research 49 (2023): 159-173.

[291]

C. Hong, A. Wang, J. Xia, et al., “Ginsenoside Rh2-Based Multifunctional Liposomes for Advanced Breast Cancer Therapy,” International Journal of Nanomedicine 19 (2024): 2879-2888.

[292]

Y. Shen, B. Zhong, W. Zheng, et al., “Rg3-Lipo Biomimetic Delivery of Paclitaxel Enhances Targeting of Tumors and Myeloid-Derived Suppressor Cells,” Journal of Clinical Investigation 134, no. 22 (2024): e178617.

[293]

Y. Xie, M. Zhu, H. Bao, et al., “Enhanced Antitumor Efficacy and Reduced Toxicity in Colorectal Cancer Using a Novel Multifunctional Rg3- Targeting Nanosystem Encapsulated With Oxaliplatin and Calcium Peroxide,” International Journal of Nanomedicine 20 (2025): 1021-1046.

[294]

J. Huang, J. Shi, N. Ma, et al., “Celastrol-Loaded Ginsenoside Rg3 Liposomes Enhance Anti-Programmed Death Ligand 1 Immunotherapy by Inducing Immunogenic Cell Death in Triple-Negative Breast Cancer,” Phytomedicine 139 (2025): 156514.

[295]

J. Xia, Z. Gan, J. Zhang, et al., “Geometric-Aware Deep Learning Enables Discovery of Bifunctional Ligand-Based Liposomes for Tumor Targeting Therapy,” Nano Today 61 (2025): 102668.

[296]

S. Liang, S. Gao, S. Fu, et al., “Screening Natural Cholesterol Analogs to Assemble Self-Adjuvant Lipid Nanoparticles for Antigens Tagging Guided Therapeutic Tumor Vaccine,” Advanced Materials (2025): e2419182, https://doi.org/10.1002/adma.202419182.

[297]

E. J. Sayour, D. Boczkowski, D. A. Mitchell, and S. K. Nair, “Cancer mRNA Vaccines: Clinical Advances and Future Opportunities,” Nature Reviews Clinical Oncology 21, no. 7 (2024): 489-500.

[298]

Z. Guo, Q. Jing, Z. Xu, D. Zhang, W. Zheng, and F. Ren, “Corosolic Acid-Modified Lipid Nanoparticles as Delivery Carriers for DNA Vaccines Against avian Influenza,” International Journal of Pharmaceutics 638 (2023): 122914.

[299]

Y. Liu, R. Zhang, Y. Yang, X. Liu, and Y. Jiang, “Corosolic Acid Derivative-Based Lipid Nanoparticles for Efficient RNA Delivery,” Journal of Controlled Release 378 (2025): 1-17.

[300]

M. Zhang, R. Zhang, C. Feng, X. Jiang, X. Xu, and J. Wang, “Ginsenoside Compound K-Based Multifunctional Liposomes for the Treatment of Rheumatoid Arthritis,” Drug Delivery 32, no. 1 (2025): 2464190.

[301]

J. Xia, S. Zhang, R. Zhang, et al., “Targeting Therapy and Tumor Microenvironment Remodeling of Triple-Negative Breast Cancer by Ginsenoside Rg3 Based Liposomes,” Journal of Nanbiotechnology 20, no. 1 (2022): 414.

[302]

H. Zhang, J. Huang, Y. Li, et al., “Celastrol-Loaded Ginsenoside Rg3 Liposomes Boost Immunotherapy by Remodeling Obesity-Related Immunosuppressive Tumor Microenvironment in Melanoma,” Acta Pharmaceutica Sinica B 15, no. 5 (2025): 2687-2702.

[303]

X. Yue, H. Guo, G. Wang, et al., “A Tailored Phytosomes Based Nose-to-brain Drug Delivery Strategy: Silver Bullet for Alzheimer's Disease,” Bioactive Materials 44 (2025): 97-115.

[304]

C. Huang, K. Gou, X. Yue, et al., “A Novel Hyaluronic Acid-Based Dissolving Microneedle Patch Loaded With Ginsenoside Rg3 Liposome for Effectively Alleviate Psoriasis,” Materials and Design 224 (2022): 111363.

[305]

W. Yang, M. Cao, W. Wang, et al., “Multifunctional Composite Soluble Microneedle Patch Based on “One Stone, Three Birds” Strategy for Promoting the Healing of Infectious Wounds,” Colloids and Surfaces B 241 (2024): 114049.

[306]

H. Tang, X. Li, C. Li, et al., “Sequential Delivery of Anti-Inflammatory and Anti-Scar Drugs by Rg3 Liposome-Embedded Thiolated Chitosan Hydrogel Eye Drops for Corneal Alkali Burn,” Carbohydrate Polymers 361 (2025): 123626.

[307]

M.-Z. Wang, T.-W. Gu, Y. Xu, L. Yang, Z.-H. Jiang, and L.-H. Peng, “Mechanical Stretching of Cells and Lipid Nanoparticles for Nucleic Acid Delivery,” Journal of Controlled Release 339 (2021): 208-219.

[308]

M. Liu, S.-T. Li, J.-H. Wang, et al., “Methotrexate-Modified Docetaxel Liposome Targeting With Ginsenoside Rh2 as a Membrane Stabilizer for the Treatment of Ovarian Cancer,” Journal of Drug Delivery Science and Technology 98 (2024): 105917.

[309]

S. Hu, D. Sun, L. Tang, et al., “Follicle-Stimulating Hormone Peptide-Conjugated Liposomes in the Treatment of Epithelial Ovarian Cancer Through the Induction of M2-to-M1 Macrophage Repolarization,” International Journal of Pharmaceutics 672 (2025): 125334.

[310]

H. Ao, H. Song, J. Li, and X. Wang, “Enhanced Anti-Glioma Activity of Annonaceous Acetogenins Based on a Novel Liposomal Co-delivery System With Ginsenoside Rh2,” Drug Delivery 31, no. 1 (2024): 2324716.

[311]

D. Huang, Z. Tang, X. Pu, T. Wang, F. Gao, and C. Li, “A Novel Cabazitaxel Liposomes Modified With Ginsenoside Rk1 for Cancer Targeted Therapy,” Acupuncture and Herbal Medicine 4, no. 1 (2024): 113-121.

[312]

F. Gong, Z. Wang, R. Mo, et al., “Nano-Sponge-Like Liposomes Remove Cholesterol Crystals for Antiatherosclerosis,” Journal of Controlled Release 349 (2022): 940-953.

[313]

Y. Wang, W. He, P. Ren, L. Zhao, D. Zheng, and J. Jin, “Carthamin Yellow-Loaded Glycyrrhetinic Acid Liposomes Alleviate Interstitial Fibrosis in Diabetic Nephropathy,” Renal Failure 47, no. 1 (2025): 2459356.

[314]

Z. Xu, Y. Huang, Y. Wu, et al., “Glycyrrhizic Acid-Lipid Framework Nanovehicle Loading Triptolide for Combined Immunochemotherapy,” ACS Applied Materials & Interfaces 15, no. 35 (2023): 41337-41350.

[315]

S. Zhang, S. Ma, S. Hao, et al., “Fucoidan-Modified Antibiotic-Free Nanovesicles: A Multidimensional Approach to Eradicate Intracellular and Extracellular Helicobacter pylori and Restore Gastrointestinal Homeostasis,” International Journal of Biological Macromolecules 307 (2025): 141786.

[316]

A. Prakash, T. Gates, and E. Lou, “Senescence-Associated Secretory Phenotype Regulation by Dual-drug Delivery Biomimetic Nanoplatform for Enhanced Tumor Chemotherapy,” Molecular Therapy: Oncology 32, no. 4 (2024): 200869.

[317]

S. Li, Y. Liu, X. Sui, et al., “Novel Tubeimoside I Liposomal Drug Delivery System in Combination With Gemcitabine for the Treatment of Pancreatic Cancer,” Nanomedicine 19, no. 24 (2024): 1977-1993.

[318]

K. Wang, L. Yang, X. Lu, et al., “Construction of Sonosensitizer-Drug Co-Assembly Based on Deep Learning Method,” Small (2025): e2502328.

[319]

C. Zhang, Y. Yuan, Q. Xia, et al., “Machine Learning-Driven Prediction, Preparation, and Evaluation of Functional Nanomedicines via Drug-Drug Self-Assembly,” Advanced Science 12, no. 9 (2025): e2415902.

[320]

J.-J. Zheng, Q.-Z. Li, Z. Wang, X. Wang, Y. Zhao, and X. Gao, “Computer-Aided Nanodrug Discovery: Recent Progress and Future Prospects,” Chemical Society Reviews 53, no. 18 (2024): 9059-9132.

[321]

P. Tan, X. Chen, H. Zhang, Q. Wei, and K. Luo, “Artificial Intelligence Aids in Development of Nanomedicines for Cancer Management,” Seminars in Cancer Biology 89 (2023): 61-75.

[322]

L. Rao, Y. Yuan, X. Shen, G. Yu, and X. Chen, “Designing Nanotheranostics With Machine Learning,” Nature Nanotechnology 19, no. 12 (2024): 1769-1781.

[323]

Y.-L. Wang, Y. Mu, Y.-L. Zhang, et al., “Accessible and Effective Nanomedicines: Self-Assembly Products from Chinese Herbal Medicines (CHMs),” Advanced Functional Materials 35, no. 9 (2025): e2416151.

[324]

X. Guo, W. Luo, L. Wu, et al., “Natural Products From Herbal Medicine Self-Assemble Into Advanced Bioactive Materials,” Advanced Science 11, no. 35 (2024): e2403388.

[325]

Y.-L. Zhang, Y.-L. Wang, K. Yan, et al., “Nanostructures in Chinese Herbal Medicines (CHMs) for Potential Therapy,” Nanoscale Horiz 8, no. 8 (2023): 976-990.

[326]

M. Zhou, R.-H. Zhang, M. Wang, G.-B. Xu, and S.-G. Liao, “Prodrugs of Triterpenoids and Their Derivatives,” European Journal of Medicinal Chemistry 131 (2017): 222-236.

RIGHTS & PERMISSIONS

2025 The Author(s). Aggregate published by SCUT, AIEI, and John Wiley & Sons Australia, Ltd.

AI Summary AI Mindmap
PDF

2

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/