Lipid-Based Nanoplatforms in Hepatology: From Rational Design to Clinical Translation Challenges

Jie Wang , Qian Zhang , Lin Yang , Zijian Cheng , Chunhong Wang , Runlin Song , Honglan Dai , Xinxin Zhang

MEDCOMM - Biomaterials and Applications ›› 2025, Vol. 4 ›› Issue (3) : e70025

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MEDCOMM - Biomaterials and Applications ›› 2025, Vol. 4 ›› Issue (3) : e70025 DOI: 10.1002/mba2.70025
REVIEW ARTICLE

Lipid-Based Nanoplatforms in Hepatology: From Rational Design to Clinical Translation Challenges

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Abstract

Liver diseases—encompassing hepatitis, liver fibrosis, fatty liver, and hepatocellular carcinoma—constitute a formidable global health challenge. Existing treatments are often limited by several key issues, such as low drug accumulation, poor selectivity for target cells, and the toxic side effects of drugs. Lipid-based nanocarriers (LBNCs) have emerged as an up-and-coming platform, leveraging their biocompatibility, versatile drug-loading capacity, and tunable targeting capabilities to overcome these limitations. This comprehensive review critically examines recent advances in the rational design of LBNCs, including liposomes, micelles, nanoemulsions, solid lipid nanoparticles, lipid nanoparticles, biomimetic lipid nanocarriers, and smart responsive lipid nanocarriers, as well as their applications in lipid materials. Subsequently, we delve into their translational application, meticulously reviewing preclinical successes and current clinical progress (encompassing active clinical trials and FDA-approved LBNC formulations). Finally, by analyzing the challenges from rational design to clinical translation, we propose forward-looking perspectives and strategic recommendations to overcome these hurdles and accelerate the realization of LBNC-based therapies in clinical hepatology. This review aims to serve as a valuable reference for researchers, providing in-depth insights into the evolving field of LBNCs and their significant therapeutic potential in hepatology.

Keywords

drug delivery systems / lipid materials / lipid-based nanocarriers / liver diseases / liver target

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Jie Wang, Qian Zhang, Lin Yang, Zijian Cheng, Chunhong Wang, Runlin Song, Honglan Dai, Xinxin Zhang. Lipid-Based Nanoplatforms in Hepatology: From Rational Design to Clinical Translation Challenges. MEDCOMM - Biomaterials and Applications, 2025, 4(3): e70025 DOI:10.1002/mba2.70025

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References

[1]

M. J. Mitchell, M. M. Billingsley, R. M. Haley, M. E. Wechsler, N. A. Peppas, and R. Langer, “Engineering Precision Nanoparticles for Drug Delivery,” Nature Reviews Drug Discovery 20, no. 2 (2021): 101–124.

[2]

S. Lanini, A. Ustianowski, R. Pisapia, A. Zumla, and G. Ippolito, “Viral Hepatitis,” Infectious Disease Clinics of North America 33, no. 4 (2019): 1045–1062.

[3]

J. M. Llovet, R. K. Kelley, A. Villanueva, et al., “Hepatocellular Carcinoma,” Nature Reviews Disease Primers 7, no. 1 (2021): 6.

[4]

T. Kisseleva and D. Brenner, “Molecular and Cellular Mechanisms of Liver Fibrosis and Its Regression,” Nature Reviews Gastroenterology & Hepatology 18, no. 3 (2021): 151–166.

[5]

J. Berumen, J. Baglieri, T. Kisseleva, and K. Mekeel, “Liver Fibrosis: Pathophysiology and Clinical Implications,” WIREs Mechanisms of Disease 13, no. 1 (2021): e1499.

[6]

H. Devarbhavi, S. K. Asrani, J. P. Arab, Y. A. Nartey, E. Pose, and P. S. Kamath, “Global Burden of Liver Disease: 2023 Update,” Journal of Hepatology 79, no. 2 (2023): 516–537.

[7]

Y. Fan, H. Xue, and H. Zheng, “Systemic Therapy for Hepatocellular Carcinoma: Current Updates and Outlook,” Journal of Hepatocellular Carcinoma 9 (2022): 233–263.

[8]

Y. Cheng, X. Chen, L. Feng, et al., “Stromal Architecture and Fibroblast Subpopulations With Opposing Effects on Outcomes in Hepatocellular Carcinoma,” Cell Discovery 11, no. 1 (2025): 1.

[9]

S. A. Salunkhe, D. Chitkara, R. I. Mahato, and A. Mittal, “Lipid Based Nanocarriers for Effective Drug Delivery and Treatment of Diabetes Associated Liver Fibrosis,” Advanced Drug Delivery Reviews 173 (2021): 394–415.

[10]

X. Song, R. Li, H. Deng, et al., “Receptor Mediated Transcytosis in Biological Barrier: The Influence of Receptor Character and Their Ligand Density on the Transmembrane Pathway of Active-Targeting Nanocarriers,” Biomaterials 180 (2018): 78–90.

[11]

Y. Zhou, Q. Ge, X. Wang, et al., “Advances in Lipid Nanoparticle-Based Disease Treatment,” ChemMedChem 20 (2025): e202400938.

[12]

N. Ying, S. Liu, M. Zhang, et al., “Nano Delivery System for Paclitaxel: Recent Advances in Cancer Theranostics,” Colloids and Surfaces B: Biointerfaces 228 (2023): 113419.

[13]

S. Yonezawa, H. Koide, and T. Asai, “Recent Advances in siRNA Delivery Mediated by Lipid-Based Nanoparticles,” Advanced Drug Delivery Reviews 154–155 (2020): 64–78.

[14]

W. Li, C. Wang, Y. Zhang, and Y. Lu, “Lipid Nanocarrier-Based mRNA Therapy: Challenges and Promise for Clinical Transformation,” Small 20, no. 28 (2024): e2310531.

[15]

X. Hou, T. Zaks, R. Langer, and Y. Dong, “Lipid Nanoparticles for mRNA Delivery,” Nature Reviews Materials 6, no. 12 (2021): 1078–1094.

[16]

T. Safra, F. Muggia, S. Jeffers, et al., “Pegylated Liposomal Doxorubicin (doxil): Reduced Clinical Cardiotoxicity in Patients Reaching or Exceeding Cumulative Doses of 500 mg/m2,” Annals of Oncology 11, no. 8 (2000): 1029–1034.

[17]

J. Gong, W. Tu, J. Liu, et al., “Hepatocytes: A Key Role in Liver Inflammation,” Frontiers in Immunology 13 (2022): 1083780.

[18]

R. F. Schwabe and D. A. Brenner, “Hepatic Stellate Cells: Balancing Homeostasis, Hepatoprotection and Fibrogenesis in Health and Disease,” Nature Reviews Gastroenterology & Hepatology 22 (2025): 481–499.

[19]

O. O. Badmus, S. A. Hillhouse, C. D. Anderson, T. D. Hinds, and D. E. Stec, “Molecular Mechanisms of Metabolic Associated Fatty Liver Disease (MAFLD): Functional Analysis of Lipid Metabolism Pathways,” Clinical Science 136, no. 18 (2022): 1347–1366.

[20]

S. Chidambaranathan-Reghupaty, P. B. Fisher, and D. Sarkar, “Hepatocellular Carcinoma (HCC): Epidemiology, Etiology and Molecular Classification,” Advances in Cancer Research 149 (2021): 1–61.

[21]

M. Peiseler, B. Araujo David, J. Zindel, et al., “Kupffer Cell-Like Syncytia Replenish Resident Macrophage Function in the Fibrotic Liver,” Science 381, no. 6662 (2023): eabq5202.

[22]

J. Gracia-Sancho, E. Caparrós, A. Fernández-Iglesias, and R. Francés, “Role of Liver Sinusoidal Endothelial Cells in Liver Diseases,” Nature Reviews Gastroenterology & Hepatology 18, no. 6 (2021): 411–431.

[23]

A. Jain, A. Jain, P. Parajuli, et al., “Recent Advances in Galactose-Engineered Nanocarriers for the Site-Specific Delivery of siRNA and Anticancer Drugs,” Drug Discovery Today 23, no. 5 (2018): 960–973.

[24]

G. Zhang, X. Jiang, Y. Xia, et al., “Hyaluronic Acid-Conjugated Lipid Nanocarriers in Advancing Cancer Therapy: A Review,” International Journal of Biological Macromolecules 299 (2025): 140146.

[25]

Y. Du, W. He, Q. Xia, W. Zhou, C. Yao, and X. Li, “Thioether Phosphatidylcholine Liposomes: A Novel ROS-Responsive Platform for Drug Delivery,” ACS Applied Materials & Interfaces 11, no. 41 (2019): 37411–37420.

[26]

L. Li, Y. Wang, Y. Xu, et al., “ROS-Scavenging Lipid-Based Liquid Crystalline as a Favorable Stem Cell Extracellular Vesicles Delivery Vector to Promote Wound Healing,” Journal of Controlled Release 371 (2024): 298–312.

[27]

B. Yan, X. Zheng, Y. Wang, et al., “Liposome-Based Silibinin for Mitigating Nonalcoholic Fatty Liver Disease: Dual Effects via Parenteral and Intestinal Routes,” ACS Pharmacology & Translational Science 6, no. 12 (2023): 1909–1923.

[28]

J. Zhang, R. Li, Q. Liu, et al., “SB431542-Loaded Liposomes Alleviate Liver Fibrosis by Suppressing TGF-β Signaling,” Molecular Pharmaceutics 17, no. 11 (2020): 4152–4162.

[29]

K. Wang, H. Chen, J. Zheng, J. Chen, Y. Chen, and Y. Yuan, “Engineered Liposomes Targeting Hepatic Stellate Cells Overcome Pathological Barriers and Reverse Liver Fibrosis,” Journal of Controlled Release 368 (2024): 219–232.

[30]

P. Luo, Q. Zhang, S. Shen, et al., “Mechanistic Engineering of Celastrol Liposomes Induces Ferroptosis and Apoptosis by Directly Targeting VDAC2 in Hepatocellular Carcinoma,” Asian Journal of Pharmaceutical Sciences 18, no. 6 (2023): 100874.

[31]

W. Teng, L. Zhao, S. Yang, et al., “The Hepatic-Targeted, Resveratrol Loaded Nanoparticles for Relief of High Fat Diet-Induced Nonalcoholic Fatty Liver Disease,” Journal of Controlled Release 307 (2019): 139–149.

[32]

Y. Li, T. Zhang, Q. Liu, et al., “Mixed Micelles Loaded With the 5-benzylidenethiazolidine-2,4-dione Derivative SKLB023 for Efficient Treatment of Non-Alcoholic Steatohepatitis,” International Journal of Nanomedicine 14 (2019): 3943–3953.

[33]

N. K. Sethiya, P. Shah, A. Rajpara, P. A. Nagar, and S. H. Mishra, “Antioxidant and Hepatoprotective Effects of Mixed Micellar Lipid Formulation of Phyllanthin and Piperine in Carbon Tetrachloride-Induced Liver Injury in Rodents,” Food & Function 6, no. 11 (2015): 3593–3603.

[34]

D. Mehta, C. Dua, R. Chakraborty, P. Yadav, U. Dasgupta, and A. Bajaj, “Docetaxel-Conjugated Bile Acid-Derived Nanomicelles Can Inhibit Tumour Progression With Reduced Toxicity,” Nanoscale Advances 7, no. 7 (2025): 2003–2010.

[35]

W. Li, C. Zhou, Y. Fu, et al., “Targeted Delivery of Hyaluronic Acid Nanomicelles to Hepatic Stellate Cells in Hepatic Fibrosis Rats,” Acta Pharmaceutica Sinica B 10, no. 4 (2020): 693–710.

[36]

R. Tao, M. Gao, F. Liu, et al., “Alleviating the Liver Toxicity of Chemotherapy via pH-Responsive Hepatoprotective Prodrug Micelles,” ACS Applied Materials & Interfaces 10, no. 26 (2018): 21836–21846.

[37]

R. Parveen, S. Baboota, J. Ali, A. Ahuja, S. S. Vasudev, and S. Ahmad, “Effects of Silymarin Nanoemulsion Against Carbon Tetrachloride-Induced Hepatic Damage,” Archives of Pharmacal Research 34, no. 5 (2011): 767–774.

[38]

H. Farouk, M. Nasr, M. A. Elbaset, M. E. Shabana, O. A. H. Ahmed-Farid, and R. F. Ahmed, “Baicalin Nanoemulsion Mitigates Cisplatin-Induced Hepatotoxicity by Alleviating Oxidative Stress, Inflammation, and Restoring Cellular Integrity,” Toxicology and Applied Pharmacology 495 (2025): 117231.

[39]

J. Hussein, M. A. El-Bana, Z. El-kHayat, M. E. El-Naggar, A. R. Farrag, and D. Medhat, “Eicosapentaenoic Acid Loaded Silica Nanoemulsion Attenuates Hepatic Inflammation Through the Enhancement of Cell Membrane Components,” Biological Procedures Online 24, no. 1 (2022): 11.

[40]

X. Niu, G. Chang, N. Xu, et al., “Vitamin A-Integrated Cinnamaldehyde Nanoemulsion: A Nanotherapeutic Approach to Counteract Liver Fibrosis via Gut-Liver Axis Modulation,” ACS Nano 19, no. 10 (2025): 10433–10451.

[41]

Z. M. Cheng, S. Xu, Y. Lei, et al., “A Novel Protein-Polysaccharide Oral Nanoemulsion Targeting Activated Hepatic Stellate Cells to Enhance the Therapeutic Effect of Pirfenidone on Fibrosis After Transarterial Chemoembolization for Liver Cancer,” Advanced Functional Materials 35, no. 24 (2025): 2411665.

[42]

Y. Fan, H. Bai, T. Liu, R. Wang, and Z. Wang, “The Role of Galactose and Chitosan in Novel Targeted Nanoemulsion Delivery Carriers: Synthesis, In Vitro Stability, and Anti-Hepa 1-6 Cell Activity,” Carbohydrate Polymers 358 (2025): 123515.

[43]

C. Medina-Montano, I. Rivero Berti, R. Gambaro, et al., “Nanostructured Lipid Carriers Loaded With Dexamethasone Prevent Inflammatory Responses in Primary Non-Parenchymal Liver Cells,” Pharmaceutics 14, no. 8 (2022): 1611.

[44]

M. Xue, L. Zhang, M. Yang, et al., “Berberine-Loaded Solid Lipid Nanoparticles Are Concentrated in the Liver and Ameliorate Hepatosteatosis in db/db Mice,” International Journal of Nanomedicine 10 (2015): 5049–5057.

[45]

W. H. Kong, K. Park, M.-Y. Lee, H. Lee, D. K. Sung, and S. K. Hahn, “Cationic Solid Lipid Nanoparticles Derived From Apolipoprotein-Free LDLs for Target Specific Systemic Treatment of Liver Fibrosis,” Biomaterials 34, no. 2 (2013): 542–551.

[46]

J. Varshosaz, A. Jafarian, G. Salehi, and B. Zolfaghari, “Comparing Different Sterol Containing Solid Lipid Nanoparticles for Targeted Delivery of Quercetin in Hepatocellular Carcinoma,” Journal of Liposome Research 24, no. 3 (2014): 191–203.

[47]

H. Zhang, F. Ding, Z. Zhu, Q. Sun, and C. Yang, “Engineered Ionizable Lipid Nanoparticles Mediated Efficient siRNA Delivery to Macrophages for Anti-Inflammatory Treatment of Acute Liver Injury,” International Journal of Pharmaceutics 631 (2023): 122489.

[48]

J. Yi, X. Lei, F. Guo, et al., “Co-Delivery of Cas9 mRNA and Guide RNAs Edits Hepatitis B Virus Episomal and Integration DNA in Mouse and Tree Shrew Models,” Antiviral Research 215, no. 1872–9096 (2023): 105618.

[49]

F. Rizvi, E. Everton, A. R. Smith, et al., “Murine Liver Repair via Transient Activation of Regenerative Pathways in Hepatocytes Using Lipid Nanoparticle-Complexed Nucleoside-Modified mRNA,” Nature Communications 12, no. 1 (2021): 613.

[50]

X. Han, J. Xu, Y. Xu, et al., “In Situ Combinatorial Synthesis of Degradable Branched Lipidoids for Systemic Delivery of mRNA Therapeutics and Gene Editors,” Nature Communications 15, no. 1 (2024): 1762.

[51]

Y. Wang, S. Li, M. Hu, et al., “Universal STING Mimic Boosts Antitumour Immunity via Preferential Activation of Tumour Control Signalling Pathways,” Nature Nanotechnology 19, no. 6 (2024): 856–866.

[52]

H. Chen, W. Yin, K. Yao, et al., “Mesenchymal Stem Cell Membrane-Camouflaged Liposomes for Biomimetic Delivery of Cyclosporine A for Hepatic Ischemia-Reperfusion Injury Prevention,” Advanced Science 11, no. 32 (2024): e2404171.

[53]

A. A. Zahid, A. Chakraborty, Y. Shamiya, R. B. Wilson, N. Borradaile, and A. Paul, “Cell Membrane-Derived Nanoparticles as Biomimetic Nanotherapeutics to Alleviate Fatty Liver Disease,” ACS Applied Materials & Interfaces 16, no. 30 (2024): 39117–39128.

[54]

S. Xia, Z. Liu, J. Cai, et al., “Liver Fibrosis Therapy Based on Biomimetic Nanoparticles Which Deplete Activated Hepatic Stellate Cells,” Journal of Controlled Release 355 (2023): 54–67.

[55]

T. Wan, J. Zhong, Q. Pan, T. Zhou, Y. Ping, and X. Liu, “Exosome-Mediated Delivery of Cas9 Ribonucleoprotein Complexes for Tissue-Specific Gene Therapy of Liver Diseases,” Science Advances 8, no. 37 (2022): eabp9435.

[56]

J. Lin, J. Chen, M. Wang, et al., “Ultrasound-Driven ROS-Scavenging Nanobubbles for Synergistic NASH Treatment via FXR Activation,” Ultrasonics Sonochemistry 118 (2025): 107352.

[57]

F. Hu, H. Yue, T. Lu, and G. Ma, “Cytosolic Delivery of HBsAg and Enhanced Cellular Immunity by pH-Responsive Liposome,” Journal of Controlled Release 324 (2020): 460–470.

[58]

E. Geervliet, S. Moreno, L. Baiamonte, et al., “Matrix metalloproteinase-1 Decorated Polymersomes, a Surface-Active Extracellular Matrix Therapeutic, Potentiates Collagen Degradation and Attenuates Early Liver Fibrosis,” Journal of Controlled Release 332 (2021): 594–607.

[59]

L. F. Zhang, W. Q. Deng, X. H. Wang, et al., “Pathological Microenvironment-Remodeling Nanoparticles to Alleviate Liver Fibrosis: Reversing Hepatocytes-Hepatic Stellate Cells Malignant Crosstalk,” Advanced Science 12, no. 4 (2025): e2408898.

[60]

S. Qin, X. Du, K. Wang, et al., “Vitamin A-Modified ZIF-8 Lipid Nanoparticles for the Therapy of Liver Fibrosis,” International Journal of Pharmaceutics 642 (2023): 123167.

[61]

J. Hong and Y. H. Kim, “Fatty Liver/Adipose Tissue Dual-Targeting Nanoparticles With Heme Oxygenase-1 Inducer for Amelioration of Obesity, Obesity-Induced Type 2 Diabetes, and Steatohepatitis,” Advanced Science 9, no. 33 (2022): e2203286.

[62]

I. Domingues, C. B. Michalowski, V. Marotti, et al., “Exploiting the Biological Effect Exerted by Lipid Nanocapsules in Non-Alcoholic Fatty Liver Disease,” Journal of Controlled Release 356 (2023): 542–553.

[63]

M. Regenold, J. Steigenberger, E. Siniscalchi, et al., “Determining Critical Parameters That Influence In Vitro Performance Characteristics of a Thermosensitive Liposome Formulation of Vinorelbine,” Journal of Controlled Release 328 (2020): 551–561.

[64]

N. Borys and M. W. Dewhirst, “Drug Development of lyso-Thermosensitive Liposomal Doxorubicin: Combining Hyperthermia and Thermosensitive Drug Delivery,” Advanced Drug Delivery Reviews 178 (2021): 113985.

[65]

M. Regenold, P. Bannigan, J. C. Evans, A. Waspe, M. J. Temple, and C. Allen, “Turning Down the Heat: The Case for Mild Hyperthermia and Thermosensitive Liposomes,” Nanomedicine: Nanotechnology, Biology, and Medicine 40 (2022): 102484.

[66]

S. You, Z. Luo, N. Cheng, et al., “Magnetically Responsive Nanoplatform Targeting circRNA circ_0058051 Inhibits Hepatocellular Carcinoma Progression,” Drug Delivery and Translational Research 13, no. 3 (2023): 782–794.

[67]

K. Singh, S. Singhal, S. Pahwa, et al., “Nanomedicine and Drug Delivery: A Comprehensive Review of Applications and Challenges,” Nano-Structures & Nano-Objects 40 (2024): 101403.

[68]

L. van der Koog, T. B. Gandek, and A. Nagelkerke, “Liposomes and Extracellular Vesicles as Drug Delivery Systems: A Comparison of Composition, Pharmacokinetics, and Functionalization,” Advanced Healthcare Materials 11, no. 5 (2022): e2100639.

[69]

P. Trucillo, R. Campardelli, and E. Reverchon, “Supercritical CO2 Assisted Liposomes Formation: Optimization of the Lipidic Layer for an Efficient Hydrophilic Drug Loading,” Journal of CO2 Utilization 18 (2017): 181–188.

[70]

K. Tahara, H. Tomida, Y. Ito, et al., “Pulmonary Liposomal Formulations Encapsulated Procaterol Hydrochloride by a Remote Loading Method Achieve Sustained Release and Extended Pharmacological Effects,” International Journal of Pharmaceutics 505, no. 1–2 (2016): 139–146.

[71]

Y. Li, R. Yao, M. Ren, et al., “Liposomes Trigger Bone Marrow Niche Macrophage ‘Foam’ Cell Formation and Affect Hematopoiesis in Mice,” Journal of Lipid Research 63, no. 10 (2022): 100273.

[72]

M. R. Maradana, S. K. Yekollu, B. Zeng, et al., “Immunomodulatory Liposomes Targeting Liver Macrophages Arrest Progression of Nonalcoholic Steatohepatitis,” Metabolism: Clinical and Experimental 78 (2018): 80–94.

[73]

M. M. AbouSamra, “Liposomal Nano-Carriers Mediated Targeting of Liver Disorders: Mechanisms and Applications,” Journal of Liposome Research 34, no. 4 (2024): 728–743.

[74]

R. Sun, D. Xu, Q. Wei, et al., “Silybin Ameliorates Hepatic Lipid Accumulation and Modulates Global Metabolism in an NAFLD Mouse Model,” Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 123 (2020): 109721.

[75]

H. Liu, N. Jiang, G. Kuang, et al., “Chrysin and Its Nanoliposome Ameliorated Non-Alcoholic Steatohepatitis via Inhibiting TLR4 Signalling Pathway,” Journal of Pharmacy and Pharmacology 75, no. 8 (2023): 1046–1057.

[76]

N. Yin, J. Pang, and X. Liu, “Exploration of the Optimal Concentration of Quercetin Liposome Nanoparticles for the Treatment of Liver Damage,” BMC Pharmacology and Toxicology 26, no. 1 (2025): 112.

[77]

J. Lee, J. Byun, G. Shim, and Y. K. Oh, “Fibroblast Activation Protein Activated Antifibrotic Peptide Delivery Attenuates Fibrosis in Mouse Models of Liver Fibrosis,” Nature Communications 13, no. 1 (2022): 1516.

[78]

Y. Li, T. Zhang, J. Zhang, et al., “Dually Fibronectin/CD44-Mediated Nanoparticles Targeted Disrupt the Golgi Apparatus and Inhibit the Hedgehog Signaling in Activated Hepatic Stellate Cells to Alleviate Liver Fibrosis,” Biomaterials 301 (2023): 122232.

[79]

Y. Lu, E. Zhang, J. Yang, and Z. Cao, “Strategies to Improve Micelle Stability for Drug Delivery,” Nano Research 11, no. 10 (2018): 4985–4998.

[80]

H. Maeda, J. Wu, T. Sawa, Y. Matsumura, and K. Hori, “Tumor Vascular Permeability and the EPR Effect in Macromolecular Therapeutics: A Review,” Journal of Controlled Release 65, no. 1–2 (2000): 271–284.

[81]

D. L. Stirland, J. W. Nichols, S. Miura, and Y. H. Bae, “Mind the Gap: A Survey of How Cancer Drug Carriers Are Susceptible to the Gap Between Research and Practice,” Journal of Controlled Release 172, no. 3 (2013): 1045–1064.

[82]

S. Jacob, A. B. Nair, S. Boddu, et al., “The Emerging Role of Lipid Nanosystems and Nanomicelles in Liver Diseases,” European Review for Medical and Pharmacological Sciences 27, no. 18 (2023): 8651–8680.

[83]

B. Ashok, L. Arleth, R. P. Hjelm, I. Rubinstein, and H. Önyüksel, “In Vitro Characterization of PEGylated Phospholipid Micelles for Improved Drug Solubilization: Effects of PEG Chain Length and PC Incorporation,” Journal of Pharmaceutical Sciences 93, no. 10 (2004): 2476–2487.

[84]

F. Dong, Y. Xie, J. Qi, et al., “Bile Salt/Phospholipid Mixed Micelle Precursor Pellets Prepared by Fluid-Bed Coating,” International Journal of Nanomedicine 8 (2013): 1653–1663.

[85]

L. Wang, M. Peng, Y. Zhu, et al., “Preparation of Pluronic/Bile Salt/Phospholipid Mixed Micelles as Drug Solubility Enhancer and Study the Effect of the PPO Block Size on the Solubility of Pyrene,” Iranian Journal of Pharmaceutical Research: IJPR 13, no. 4 (2014): 1157–1163.

[86]

Y. Ikeda, S. Morita, and T. Terada, “Cholesterol Attenuates Cytoprotective Effects of Phosphatidylcholine Against Bile Salts,” Scientific Reports 7, no. 1 (2017): 306.

[87]

H. Zhang, Z. He, C. Fu, et al., “Dissociation of Polymeric Micelle Under Hemodynamic Shearing,” Nano Today 45 (2022): 101517.

[88]

H. Cabral and K. Kataoka, “Progress of Drug-Loaded Polymeric Micelles Into Clinical Studies,” Journal of Controlled Release 190 (2014): 465–476.

[89]

N. Nishiyama and K. Kataoka, “Current State, Achievements, and Future Prospects of Polymeric Micelles as Nanocarriers for Drug and Gene Delivery,” Pharmacology & Therapeutics 112, no. 3 (2006): 630–648.

[90]

A. M. Nasr, S. M. Aboelenin, M. Y. Alfaifi, et al., “Quaternized Chitosan Thiol Hydrogel-Thickened Nanoemulsion: A Multifunctional Platform for Upgrading the Topical Applications of Virgin Olive Oil,” Pharmaceutics 14, no. 7 (2022): 1319.

[91]

Y. Ozogul, G. T. Karsli, M. Durmuş, et al., “Recent Developments in Industrial Applications of Nanoemulsions,” Advances in Colloid and Interface Science 304 (2022): 102685.

[92]

M. Kumar, R. S. Bishnoi, A. K. Shukla, and C. P. Jain, “Techniques for Formulation of Nanoemulsion Drug Delivery System: A Review,” Preventive Nutrition and Food Science 24, no. 3 (2019): 225–234.

[93]

M. M. Mehanna and A. T. Mneimneh, “Formulation and Applications of Lipid-Based Nanovehicles: Spotlight on Self-Emulsifying Systems,” Advanced Pharmaceutical Bulletin 11, no. 1 (2021): 56–67.

[94]

J. F. Qiu, K. L. Zhang, X. J. Zhang, et al., “Abnormalities in Plasma Phospholipid Fatty Acid Profiles of Patients With Hepatocellular Carcinoma,” Lipids 50, no. 10 (2015): 977–985.

[95]

L. Zhang, C. Han, M. Liu, et al., “The Formation, Stability of DHA/EPA Nanoemulsion Prepared by Emulsion Phase Inversion Method and Its Application in Apple Juice,” Food Research International 133 (2020): 109132.

[96]

A. Inoue-Yamauchi, H. Itagaki, and H. Oda, “Eicosapentaenoic Acid Attenuates Obesity-Related Hepatocellular Carcinogenesis,” Carcinogenesis 39, no. 1 (2018): 28–35.

[97]

S.-N. Ju, H.-H. Shi, J.-Y. Yang, et al., “Characterization, Stability, Digestion and Absorption of a Nobiletin Nanoemulsion Using DHA-Enriched Phosphatidylcholine as an Emulsifier In Vivo and In Vitro,” Food Chemistry 397 (2022): 133787.

[98]

S. Mazzaferro, K. Bouchemal, and G. Ponchel, “Oral Delivery of Anticancer Drugs III: Formulation Using Drug Delivery Systems,” Drug Discovery Today 18, no. 1–2 (2013): 99–104.

[99]

A. Gordillo-Galeano and C. E. Mora-Huertas, “Solid Lipid Nanoparticles and Nanostructured Lipid Carriers: A Review Emphasizing on Particle Structure and Drug Release,” European Journal of Pharmaceutics and Biopharmaceutics 133 (2018): 285–308.

[100]

Y. Mirchandani, V. B. Patravale, and B. S., “Solid Lipid Nanoparticles for Hydrophilic Drugs,” Journal of Controlled Release 335 (2021): 457–464.

[101]

Y. N. Zhang, W. Poon, A. J. Tavares, I. D. McGilvray, and W. C. W. Chan, “Nanoparticle-Liver Interactions: Cellular Uptake and Hepatobiliary Elimination,” Journal of Controlled Release 240 (2016): 332–348.

[102]

B. García-Pinel, C. Porras-Alcalá, A. Ortega-Rodríguez, et al., “Lipid-Based Nanoparticles: Application and Recent Advances in Cancer Treatment,” Nanomaterials 9, no. 4 (2019): 638.

[103]

J. Mall, N. Naseem, M. F. Haider, M. A. Rahman, S. Khan, and S. N. Siddiqui, “Nanostructured Lipid Carriers as a Drug Delivery System: A Comprehensive Review With Therapeutic Applications,” Intelligent Pharmacy, ahead of print, September 23, 2024.

[104]

J. Wang, W. Pan, Y. Wang, et al., “Enhanced Efficacy of Curcumin With Phosphatidylserine-Decorated Nanoparticles in the Treatment of Hepatic Fibrosis,” Drug Delivery 25, no. 1 (2018): 1–11.

[105]

K. Mrksich, M. S. Padilla, and M. J. Mitchell, “Breaking the Final Barrier: Evolution of Cationic and Ionizable Lipid Structure in Lipid Nanoparticles to Escape the Endosome,” Advanced Drug Delivery Reviews 214 (2024): 115446.

[106]

X. Han, N. Gong, L. Xue, et al., “Ligand-Tethered Lipid Nanoparticles for Targeted RNA Delivery to Treat Liver Fibrosis,” Nature Communications 14, no. 1 (2023): 75.

[107]

N. Dammes, M. Goldsmith, S. Ramishetti, et al., “Conformation-Sensitive Targeting of Lipid Nanoparticles for RNA Therapeutics,” Nature Nanotechnology 16, no. 9 (2021): 1030–1038.

[108]

S. Liu, Y. Wen, X. Shan, et al., “Charge-Assisted Stabilization of Lipid Nanoparticles Enables Inhaled mRNA Delivery for Mucosal Vaccination,” Nature Communications 15, no. 1 (2024): 9471.

[109]

X. Han, M. G. Alameh, N. Gong, et al., “Fast and Facile Synthesis of Amidine-Incorporated Degradable Lipids for Versatile mRNA Delivery In Vivo,” Nature Chemistry 16, no. 10 (2024): 1687–1697.

[110]

Z. Gan, M. P. Lokugamage, M. Z. C. Hatit, et al., “Nanoparticles Containing Constrained Phospholipids Deliver mRNA to Liver Immune Cells In Vivo Without Targeting Ligands,” Bioengineering & Translational Medicine 5, no. 3 (2020): e10161.

[111]

L. T. Johnson, D. Zhang, K. Zhou, et al., “Lipid Nanoparticle (LNP) Chemistry Can Endow Unique In Vivo RNA Delivery Fates Within the Liver That Alter Therapeutic Outcomes in a Cancer Model,” Molecular Pharmaceutics 19, no. 11 (2022): 3973–3986.

[112]

K. Mahmoud, S. Swidan, M. El-Nabarawi, and M. Teaima, “Lipid Based Nanoparticles as a Novel Treatment Modality for Hepatocellular Carcinoma: A Comprehensive Review on Targeting and Recent Advances,” Journal of Nanobiotechnology 20, no. 1 (2022): 109.

[113]

R. Chu, Y. Wang, J. Kong, T. Pan, Y. Yang, and J. He, “Lipid Nanoparticles as the Drug Carrier for Targeted Therapy of Hepatic Disorders,” Journal of Materials Chemistry B 12, no. 20 (2024): 4759–4784.

[114]

C. Lin, A. Jans, J. C. Wolters, et al., “Targeting Ligand Independent Tropism of siRNA-LNP by Small Molecules for Directed Therapy of Liver or Myeloid Immune Cells,” Advanced Healthcare Materials 13, no. 26 (2024): 2202670.

[115]

Q. Wang, Q. Jiang, D. Li, et al., “Elaborately Engineering of Lipid Nanoparticle for Targeting Delivery of siRNA and Suppressing Acute Liver Injury,” Chinese Chemical Letters 35, no. 2 (2024): 108683.

[116]

C. Zhang, Y. Teng, X. Bai, et al., “Prevent and Reverse Metabolic Dysfunction-Associated Steatohepatitis and Hepatic Fibrosis via mRNA-Mediated Liver-Specific Antibody Therapy,” ACS Nano 18, no. 50 (2024): 34375–34390.

[117]

H. Tanaka, T. Takahashi, M. Konishi, et al., “Self-Degradable Lipid-Like Materials Based on “Hydrolysis Accelerated by the Intra-Particle Enrichment of Reactant (HyPER)” for Messenger RNA Delivery,” Advanced Functional Materials 30, no. 34 (2020): 1910575.

[118]

H. Akita, “Development of an SS-Cleavable pH-Activated Lipid-Like Material (ssPalm) as a Nucleic Acid Delivery Device,” Biological and Pharmaceutical Bulletin 43, no. 11 (2020): 1617–1625.

[119]

R. Banerjee, P. Tyagi, S. Li, and L. Huang, “Anisamide-Targeted Stealth Liposomes: A Potent Carrier for Targeting Doxorubicin to Human Prostate Cancer Cells,” International Journal of Cancer 112, no. 4 (2004): 693–700.

[120]

P. Dash, A. M. Piras, and M. Dash, “Cell Membrane Coated Nanocarriers—An Efficient Biomimetic Platform for Targeted Therapy,” Journal of Controlled Release 327 (2020): 546–570.

[121]

D. Wang, S. Jiang, F. Zhang, et al., “Cell Membrane Vesicles With Enriched CXCR4 Display Enhances Their Targeted Delivery as Drug Carriers to Inflammatory Sites,” Advanced Science 8, no. 23 (2021): e2101562.

[122]

X. Zhou, Y. Miao, Y. Wang, et al., “Tumour-Derived Extracellular Vesicle Membrane Hybrid Lipid Nanovesicles Enhance siRNA Delivery by Tumour-Homing and Intracellular Freeway Transportation,” Journal of Extracellular Vesicles 11, no. 3 (2022): e12198.

[123]

J. Wang, Z. Zhang, Y. Zhuo, et al., “Endoplasmic Reticulum-Targeted Delivery of Celastrol and PD-L1 siRNA for Reinforcing Immunogenic Cell Death and Potentiating Cancer Immunotherapy,” Acta Pharmaceutica Sinica B 14, no. 8 (2024): 3643–3660.

[124]

S. Li, F. Cheng, Z. Zhang, R. Xu, H. Shi, and Y. Yan, “The Role of Hepatocyte-Derived Extracellular Vesicles in Liver and Extrahepatic Diseases,” Biomedicine & Pharmacotherapy 180 (2024): 117502.

[125]

Y. Miao, Y. Yang, L. Guo, et al., “Cell Membrane-Camouflaged Nanocarriers With Biomimetic Deformability of Erythrocytes for Ultralong Circulation and Enhanced Cancer Therapy,” ACS Nano 16, no. 4 (2022): 6527–6540.

[126]

J. Wang, H. Pan, J. Li, et al., “Cell Membrane-Coated Mesoporous Silica Nanorods Overcome Sequential Drug Delivery Barriers Against Colorectal Cancer,” Chinese Chemical Letters 34, no. 6 (2023): 107828.

[127]

J. Li, H. Wu, Z. Yu, et al., “Hematopoietic Stem and Progenitor Cell Membrane-Coated Vesicles for Bone Marrow-Targeted Leukaemia Drug Delivery,” Nature Communications 15, no. 1 (2024): 5689.

[128]

Q. V. Le, J. Lee, H. Lee, G. Shim, and Y. K. Oh, “Cell Membrane-Derived Vesicles for Delivery of Therapeutic Agents,” Acta Pharmaceutica Sinica B 11, no. 8 (2021): 2096–2113.

[129]

H. He, C. Guo, W. Liu, S. Chen, X. Y. Wang, and H. Yang, “Engineering Nanostructured Pure Cancer Cell Membrane-Derived Vesicles as a Novel Therapeutic Cancer Vaccine,” MedComm – Biomaterials and Applications 1, no. 2 (2022): e22.

[130]

L. Zhu, Y. Zhong, S. Wu, et al., “Cell Membrane Camouflaged Biomimetic Nanoparticles: Focusing on Tumor Theranostics,” Materials Today Bio 14 (2022): 100228.

[131]

K. Wu, M. He, B. Mao, et al., “Enhanced Delivery of CRISPR/Cas9 System Based on Biomimetic Nanoparticles for Hepatitis B Virus Therapy,” Journal of Controlled Release 374 (2024): 293–311.

[132]

Y. Yang, Q. Liu, M. Wang, et al., “Genetically Programmable Cell Membrane-Camouflaged Nanoparticles for Targeted Combination Therapy of Colorectal Cancer,” Signal Transduction and Targeted Therapy 9, no. 1 (2024): 158.

[133]

X. Lin, L. Yue, K. Cheng, and L. Rao, “Engineering Cellular Vesicles for Immunotherapy,” Accounts of Materials Research 6, no. 3 (2025): 327–339.

[134]

E. Ren, C. Liu, P. Lv, J. Wang, and G. Liu, “Genetically Engineered Cellular Membrane Vesicles as Tailorable Shells for Therapeutics,” Advanced Science 8, no. 21 (2021): e2100460.

[135]

R. Kalluri and V. S. LeBleu, “The Biology, Function, and Biomedical Applications of Exosomes,” Science 367, no. 6478 (2020): eaau6977.

[136]

D. A. Borrelli, K. Yankson, N. Shukla, G. Vilanilam, T. Ticer, and J. Wolfram, “Extracellular Vesicle Therapeutics for Liver Disease,” Journal of Controlled Release 273 (2018): 86–98.

[137]

L. Pourtalebi Jahromi and G. Fuhrmann, “A Chemical Toolbox for Surface Engineering of Extracellular Vesicles,” Nature Reviews Bioengineering 3 (2025): 617–619.

[138]

M. Tian, X. Xin, R. Wu, W. Guan, and W. Zhou, “Advances in Intelligent-Responsive Nanocarriers for Cancer Therapy,” Pharmacological Research 178 (2022): 106184.

[139]

D. Singh, Y. Sharma, D. Dheer, and R. Shankar, “Stimuli Responsiveness of Recent Biomacromolecular Systems (Concept to Market): A Review,” International Journal of Biological Macromolecules 261, no. Pt 2 (2024): 129901.

[140]

L. Mao, P. Ma, X. Luo, et al., “Stimuli-Responsive Polymeric Nanovaccines Toward Next-Generation Immunotherapy,” ACS Nano 17, no. 11 (2023): 9826–9849.

[141]

M. Z. Jin and W. L. Jin, “The Updated Landscape of Tumor Microenvironment and Drug Repurposing,” Signal Transduction and Targeted Therapy 5, no. 1 (2020): 166.

[142]

F. D. Moghaddam, E. N. Zare, M. Hassanpour, et al., “Chitosan-Based Nanosystems for Cancer Diagnosis and Therapy: Stimuli-Responsive, Immune Response, and Clinical Studies,” Carbohydrate Polymers 330 (2024): 121839.

[143]

D. Ezhilarasan and M. Najimi, “Intercellular Communication Among Liver Cells in the Perisinusoidal Space of the Injured Liver: Pathophysiology and Therapeutic Directions,” Journal of Cellular Physiology 238, no. 1 (2023): 70–81.

[144]

C. Gribben, V. Galanakis, A. Calderwood, et al., “Acquisition of Epithelial Plasticity in Human Chronic Liver Disease,” Nature 630, no. 8015 (2024): 166–173.

[145]

R. Bottger, G. Pauli, P. H. Chao, et al., “Lipid-Based Nanoparticle Technologies for Liver Targeting,” Advanced Drug Delivery Reviews 154–155 (2020): 79–101.

[146]

C. Ding, C. Chen, X. Zeng, H. Chen, and Y. Zhao, “Emerging Strategies in Stimuli-Responsive Prodrug Nanosystems for Cancer Therapy,” ACS Nano 16, no. 9 (2022): 13513–13553.

[147]

X. Meng, Y. Shen, H. Zhao, X. Lu, Z. Wang, and Y. Zhao, “Redox-Manipulating Nanocarriers for Anticancer Drug Delivery: A Systematic Review,” Journal of Nanobiotechnology 22, no. 1 (2024): 587.

[148]

P. J. Trivedi, G. M. Hirschfield, D. H. Adams, and J. M. Vierling, “Immunopathogenesis of Primary Biliary Cholangitis, Primary Sclerosing Cholangitis and Autoimmune Hepatitis: Themes and Concepts,” Gastroenterology 166, no. 6 (2024): 995–1019.

[149]

X. Liu, Z. Wu, C. Guo, et al., “Hypoxia Responsive Nano-Drug Delivery System Based on Angelica Polysaccharide for Liver Cancer Therapy,” Drug Delivery 29, no. 1 (2022): 138–148.

[150]

B. W. Duan, Y. J. Liu, X. N. Li, et al., “An Autologous Macrophage-Based Phenotypic Transformation-Collagen Degradation System Treating Advanced Liver Fibrosis,” Advanced Science 11, no. 7 (2024): e2306899.

[151]

L. Shan, F. Wang, D. Zhai, X. Meng, J. Liu, and X. Lv, “Matrix Metalloproteinases Induce Extracellular Matrix Degradation Through Various Pathways to Alleviate Hepatic Fibrosis,” Biomedicine & Pharmacotherapy 161 (2023): 114472.

[152]

B. Mackowiak, Y. Fu, L. Maccioni, and B. Gao, “Alcohol-Associated Liver Disease,” Journal of Clinical Investigation 134, no. 3 (2024): e176345.

[153]

M. Thiele, I. F. Villesen, L. Niu, et al., “Opportunities and Barriers in Omics-Based Biomarker Discovery for Steatotic Liver Diseases,” Journal of Hepatology 81, no. 2 (2024): 345–359.

[154]

M. Israelsen, S. Francque, E. A. Tsochatzis, and A. Krag, “Steatotic Liver Disease,” Lancet 404, no. 10464 (2024): 1761–1778.

[155]

J. Lin, D. Rao, M. Zhang, and Q. Gao, “Metabolic Reprogramming in the Tumor Microenvironment of Liver Cancer,” Journal of Hematology & Oncology 17, no. 1 (2024): 6.

[156]

M. S. Zhang, J. D. Cui, D. Lee, et al., “Hypoxia-Induced Macropinocytosis Represents a Metabolic Route for Liver Cancer,” Nature Communications 13, no. 1 (2022): 954.

[157]

A. J. D. S. Sanchez, D. Loughrey, E. S. Echeverri, et al., “Substituting Poly(ethylene glycol) Lipids With Poly(2-ethyl-2-oxazoline) Lipids Improves Lipid Nanoparticle Repeat Dosing,” Advanced Healthcare Materials 13, no. 17 (2024): e2304033.

[158]

L. Yu, M. Zhang, J. He, X. Sun, and P. Ni, “A Nanomedicine Composed of Polymer-ss-DOX and Polymer-Ce6 Prodrugs With Monoclonal Antibody Targeting Effect for Anti-Tumor Chemo-Photodynamic Synergetic Therapy,” Acta Biomaterialia 179 (2024): 272–283.

[159]

K. Shang, L. Zhang, Y. Yu, et al., “Disulfide-Containing Polymer Delivery of C527 and a Platinum(IV) Prodrug Selectively Inhibited Protein Ubiquitination and Tumor Growth on Cisplatin Resistant and Patient-Derived Liver Cancer Models,” Materials Today Bio 18 (2023): 100548.

[160]

D. Haemmerich, K. K. Ramajayam, and D. A. Newton, “Review of the Delivery Kinetics of Thermosensitive Liposomes,” Cancers 15, no. 2 (2023): 398.

[161]

K. Aloss, S. M. Z. Bokhari, P. H. Leroy Viana, et al., “Modulated Electro-Hyperthermia Accelerates Tumor Delivery and Improves Anticancer Activity of Doxorubicin Encapsulated in Lyso-Thermosensitive Liposomes in 4T1-Tumor-Bearing Mice,” International Journal of Molecular Sciences 25, no. 6 (2024): 3101.

[162]

D. Yang, D. Liu, H. Deng, et al., “Transferrin Functionization Elevates Transcytosis of Nanogranules Across Epithelium by Triggering Polarity-Associated Transport Flow and Positive Cellular Feedback Loop,” ACS Nano 13, no. 5 (2019): 5058–5076.

[163]

A. Wang-Gillam, N. Thakkar, A. C. Lockhart, et al., “A Phase I Study of Pegylated Liposomal Doxorubicin and Temsirolimus in Patients With Refractory Solid Malignancies,” Cancer Chemotherapy and Pharmacology 74, no. 2 (2014): 419–426.

[164]

K. T. Park, C. Nespor, and J. Kerner, , “The Use of Omegaven in Treating Parenteral Nutrition-Associated Liver Disease,” Journal of Perinatology 31, no. Suppl 1 (2011): S57–S60.

[165]

B. Li, “Prophylactic Use of Antibiotics for Postsurgical Infection in c-TACE and DEB-TACE High-Risk Patients: A Case-Control Study,” Journal of Healthcare Engineering 2022 (2022): 6203817.

[166]

J. Healthcare Engineering, “Retracted: Prophylactic Use of Antibiotics for Postsurgical Infection in c-TACE and DEB-TACE High-Risk Patients: A Case-Control Study,” Journal of Healthcare Engineering 2023 (2023): 9849480.

[167]

D. Qiao, Y. Chen, and L. Liu, “Engineered Therapeutic Nanovaccine Against Chronic Hepatitis B Virus Infection,” Biomaterials 269 (2021): 120674.

[168]

J. Chen, W. Senapedis, S. Siecinski, et al., “Abstract 2417: Detection and Quantification of Site-Specific DNA Methylation From Liquid Biopsies as a Pharmacodynamic Biomarker of OTX-2002, a Novel MYC-Targeting Epigenomic mRNA Therapeutic,” Cancer Research 84, no. 6_Suppl (2024): 2417.

[169]

D. Erion, S. Gottschalk, K. Su, et al., “KRRO-110, an RNA Editing Oligonucleotide Encapsulated in a Lipid Nanoparticle (LNP) Delivered to Liver Cells for the Treatment of Alpha-1 Antitrypsin Deficiency (AATD),” American Journal of Respiratory and Critical Care 209 (2024): A3797.

[170]

P. C. Lyon, M. D. Gray, C. Mannaris, et al., “Safety and Feasibility of Ultrasound-Triggered Targeted Drug Delivery of Doxorubicin From Thermosensitive Liposomes in Liver Tumours (TARDOX): A Single-Centre, Open-Label, Phase 1 Trial,” Lancet Oncology 19, no. 8 (2018): 1027–1039.

[171]

M. D. Gray, P. C. Lyon, C. Mannaris, et al., “Focused Ultrasound Hyperthermia for Targeted Drug Release From Thermosensitive Liposomes: Results From a Phase I Trial,” Radiology 291, no. 1 (2019): 232–238.

[172]

S. M. Hosseinikhah, L. Farhoudi, F. Mirzavi, et al., “Ultrasound-Assisted Efficient Targeting of Doxorubicin to the Tumor Microenvironment by Lyso-Thermosensitive Liposomes of Varying Phase Transition Temperatures,” European Journal of Pharmaceutical Sciences 206 (2025): 107024.

[173]

K. Aloss and P. Hamar, “Recent Preclinical and Clinical Progress in Liposomal Doxorubicin,” Pharmaceutics 15, no. 3 (2023): 893.

[174]

W. Y. Tak, S. M. Lin, Y. Wang, et al., “Phase III HEAT Study Adding Lyso-Thermosensitive Liposomal Doxorubicin to Radiofrequency Ablation in Patients With Unresectable Hepatocellular Carcinoma Lesions,” Clinical Cancer Research 24, no. 1 (2018): 73–83.

[175]

P. Merle, J. F. Blanc, J. M. Phelip, et al., “Doxorubicin-Loaded Nanoparticles for Patients With Advanced Hepatocellular Carcinoma After Sorafenib Treatment Failure (RELIVE): A Phase 3 Randomised Controlled Trial,” Lancet Gastroenterology & Hepatology 4, no. 6 (2019): 454–465.

[176]

M. Yu, Y. Yang, C. Zhu, S. Guo, and Y. Gan, “Advances in the Transepithelial Transport of Nanoparticles,” Drug Discovery Today 21, no. 7 (2016): 1155–1161.

[177]

W. Li, R. Yan, Y. Liu, et al., “Co-Delivery of Bmi1 Small Interfering RNA With Ursolic Acid by Folate Receptor-Targeted Cationic Liposomes Enhances Anti-Tumor Activity of Ursolic Acid In Vitro and In Vivo,” Drug Delivery 26, no. 1 (2019): 794–802.

[178]

Z. Zhu, Z. Qian, Z. Yan, et al., “A Phase I Pharmacokinetic Study of Ursolic Acid Nanoliposomes in Healthy Volunteers and Patients With Advanced Solid Tumors,” International Journal of Nanomedicine 8 (2013): 129–136.

[179]

S. Ogholikhan and K. Schwarz, “Hepatitis Vaccines,” Vaccines 4, no. 1 (2016): 6.

[180]

V. D'Acremont, C. Herzog, and B. Genton, “Immunogenicity and Safety of a Virosomal Hepatitis A Vaccine (Epaxal) in the Elderly,” Journal of Travel Medicine 13, no. 2 (2006): 78–83.

[181]

M. Boulin, A. Schmitt, E. Delhom, et al., “Improved Stability of Lipiodol-Drug Emulsion for Transarterial Chemoembolisation of Hepatocellular Carcinoma Results in Improved Pharmacokinetic Profile: Proof of Concept Using Idarubicin,” European Radiology 26, no. 2 (2016): 601–609.

[182]

I. Raber and A. Asnani, “Cardioprotection in Cancer Therapy: Novel Insights With Anthracyclines,” Cardiovascular Research 115, no. 5 (2019): 915–921.

[183]

R. Qi, J. Cao, Y. Wu, et al., “Combination Therapy of Therapeutic Antibody and Vaccine or Entecavir in HBV Carrier Mice,” Frontiers in Microbiology 14 (2023): 1173061.

[184]

Y. Q. Dai and L. Yu, “Efficacy of Entecavir Combined With HbsAg Nanoemulsion in the Treatment of Chronic Hepatitis B,” Journal of Modern Medicine and Health 34, no. 22 (2018): 3537–3539.

[185]

K. Tajiri, Y. Hayashi, A. Murayama, N. Muraishi, M. Minemura, and I. Yasuda, “Decrease in HBsAg After TAF Switching From Entecavir During Long-Term Treatment of Chronic Hepatitis B Virus Infection,” Viruses 17, no. 1 (2024): 44.

[186]

Y. Huang, S. Liu, X. Zhang, et al., “1342 Organ-Specific Delivery of a mRNA-Encoded Bispecific T Cell Engager Targeting Glypican-3 in Hepatocellular Carcinoma,” Journal for Immunotherapy of Cancer 12, no. Suppl 2 (2024): A1499.

[187]

I. I. Rodriguez-Rivera, T. H. Wu, R. Ciotti, et al., “A Phase 1/2 Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of OTX-2002 as a Single Agent and in Combination With Standard of Care in Patients With Hepatocellular Carcinoma and Other Solid Tumor Types Known for Association With the MYC Oncogene (MYCHELANGELO I),” Journal of Clinical Oncology 41 (2023): TPS627.

[188]

M. Chaudhry, P. Lyon, C. Coussios, and R. Carlisle, “Thermosensitive Liposomes: A Promising Step Toward Localised Chemotherapy,” Expert Opinion on Drug Delivery 19, no. 8 (2022): 899–912.

[189]

T. Sheth, S. Seshadri, T. Prileszky, and M. E. Helgeson, “Multiple Nanoemulsions,” Nature Reviews Materials 5, no. 3 (2020): 214–228.

[190]

S. Kim, S. H. Park, S. Jeong, G. Song, S. S. Oh, and G. R. Yi, “Scalable Production of Uniform Gene-Loaded Lipid Nanoparticles via a Fluidity-Controlled Membrane Extrusion,” Journal of Colloid and Interface Science 687 (2025): 74–84.

[191]

C. Glader, R. Jeitler, Y. Wang, et al., “Establishment of a Semi-Continuous Nano-Production Line Using the Microfluidizer® Technology for the Fabrication of Lipid-Based Nanoparticles Part 1: Screening of Critical Parameters and Design of Experiment Optimization Studies,” European Journal of Pharmaceutical Sciences 203 (2024): 106928.

[192]

R. Kedmi, N. Ben-Arie, and D. Peer, “The Systemic Toxicity of Positively Charged Lipid Nanoparticles and the Role of Toll-Like Receptor 4 in Immune Activation,” Biomaterials 31, no. 26 (2010): 6867–6875.

[193]

G. T. Kozma, T. Shimizu, T. Ishida, and J. Szebeni, “Anti-PEG Antibodies: Properties, Formation, Testing and Role in Adverse Immune Reactions to PEGylated Nano-Biopharmaceuticals,” Advanced Drug Delivery Reviews 154–155 (2020): 163–175.

[194]

J. Witten, I. Raji, R. S. Manan, et al., “Artificial Intelligence-Guided Design of Lipid Nanoparticles for Pulmonary Gene Therapy,” Nature Biotechnology, ahead of print, December 10, 2024.

[195]

B. Li, I. O. Raji, A. G. R. Gordon, et al., “Accelerating Ionizable Lipid Discovery for mRNA Delivery Using Machine Learning and Combinatorial Chemistry,” Nature Materials 23, no. 7 (2024): 1002–1008.

[196]

E. Moradi, S. Jalili-Firoozinezhad, and M. Solati-Hashjin, “Microfluidic Organ-on-a-Chip Models of Human Liver Tissue,” Acta Biomaterialia 116 (2020): 67–83.

[197]

T. Ching, Y. C. Toh, M. Hashimoto, and Y. S. Zhang, “Bridging the Academia-to-Industry Gap: Organ-on-a-Chip Platforms for Safety and Toxicology Assessment,” Trends in Pharmacological Sciences 42, no. 9 (2021): 715–728.

[198]

H. Xu, P. She, B. Ma, Z. Zhao, G. Li, and Y. Wang, “ROS Responsive Nanoparticles Loaded With Lipid-Specific Aiegen for Atherosclerosis-Targeted Diagnosis and Bifunctional Therapy,” Biomaterials 288 (2022): 121734.

[199]

V. D. Nguyen, S. Zheng, J. Han, V. H. Le, J. O. Park, and S. Park, “Nanohybrid Magnetic Liposome Functionalized With Hyaluronic Acid for Enhanced Cellular Uptake and Near-Infrared-Triggered Drug Release,” Colloids and Surfaces B: Biointerfaces 154 (2017): 104–114.

[200]

Y. Liu, M. Li, J. Gu, et al., “Engineering of Exosome-Liposome Hybrid-Based Theranostic Nanomedicines for NIR-II Fluorescence Imaging-Guided and Targeted NIR-II Photothermal Therapy of Subcutaneous Glioblastoma,” Colloids and Surfaces B: Biointerfaces 245 (2025): 114258.

[201]

L. Xue, X. Xiong, G. Zhao, et al., “Multiarm-Assisted Design of Dendron-Like Degradable Ionizable Lipids Facilitates Systemic mRNA Delivery to the Spleen,” Journal of the American Chemical Society 147, no. 2 (2025): 1542–1552.

[202]

A. Giordano, A. C. Provenza, G. Reverchon, L. Baldino, and E. Reverchon, “Lipid-Based Nanocarriers: Bridging Diagnosis and Cancer Therapy,” Pharmaceutics 16, no. 9 (2024): 1158.

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