Advanced strategies of covalent organic framework nanomedicines in targeting and overcoming biological barriers

Abstract

Covalent organic frameworks (COFs) are crystalline and porous materials formed from periodically organized organic molecules bonded covalently to create highly stable architectures. Their mechanical properties can be precisely adjusted through structural modifications, making COFs exceptionally suitable for applications in cancer treatment and drug delivery. This review summarizes strategies for controlling the mechanical properties of COFs, including adjustments in structural dimensions, pore sizes and host-guest interactions. The remarkable advancements in drug delivery, cancer therapy, photodynamic therapy and photothermal therapy achieved through COFs with tunable mechanical properties are then discussed. By providing deeper insights into the biomedical applications of COF systems, this review aims to foster interdisciplinary research combining nanomedicine and COF materials. Additionally, the review explores recent studies and discoveries on COFs' potential as innovative drug carriers capable of biological overcoming barriers such as the blood-brain barrier, nasal mucosa, cutaneous layers and oral mucosa. Greater insight into both the limitations and potential of COFs could pave the way for developing more effective and targeted strategies within this challenging field.

Keywords

Covalent organic frameworks (COFS) / Drug carrier / Cancer therapy / Biocompatibility / Biological Barriers

Conflicts of interest

The authors declare that there is no conflicts of interest. Written informed consent for publication was obtained from all participants.

References

[1] Abd Elkodous M, El-Sayyad GS, Abdelrahman IY, EI-Bastawisy HS, Mohamed AE, Mosallam FM, et al. Therapeutic and diagnostic potential of nanomaterials for enhanced biomedical applications. Colloids Surf B Biointerfaces 2019; 180:411-28.

[2] Valenzuela C, Chen C, Sun M, Ye Z, Zhang J. Strategies and applications of covalent organic frameworks as promising nanoplatforms in cancer therapy. J Mater Chem B 2021; 9:3450-83.

[3] Scicluna MC, Vella-Zarb L. Evolution of nanocarrier drug-delivery systems and recent advancements in covalent organic framework-drug systems. ACS Appl Nano Mater 2020;3:3097 3015.

[4] Feng L, Qian C, Zhao Y. Recent advances in covalent organic framework-based nanosystems for bioimaging and therapeutic applications. ACS Mater Lett 2020; 2:1074-92.

[5] Bhunia S, Deo KA. Gaharwar AK. 2D covalent organic frameworks for biomedical applications. Adv Funct Mater 2020; 30:2002046.

[6] Liu R, Tan KT, Gong Y, Chen Y, Li Z, Xie S, et al. Covalent organic frameworks: an ideal platform for designing ordered materials and advanced applications. Chem Soc Rev 2021; 50:120-42.

[7] Sharma RK, Yadav P, Yadav M, Gupta R, Rana P, Srivastava A, et al. Recent development of covalent organic frameworks (COFs): synthesis and catalytic (organic-electro-photo) applications. Mater Horiz 2020; 7:411-54.

[8] Gatou MA, Bika P, Stergiopoulos T, Dallas P, Pavlatou EA. Recent advances in covalent organic frameworks for heavy metal removal applications. Energies 2021;14: 3197.

[9] Yang Y, Shen Y, Wang L, Song Y, Wang L. Three-dimensional porous carbon/covalent-organic framework films integrated electrode for electrochemical sensors. J Electroanal Chem 2019; 855:113590.

[10] Altaf A, Baig N, Sohail M, Sher M, Ul-Hamid A, Altaf M. Covalent organic frameworks: advances in synthesis and applications. Mater Today Commun 2021;28: 102612.

[11] Zhan Z, Liu Y, Wang W, Du G, Cai S, Wang P. Atomic-level imaging of beam-sensitive COFs and MOFs by low-dose electron microscopy. Nanoscale Horiz 2024; 9:900-33.

[12] Machado TF, Serra MES, Murtinho D, Valente AJ, Naushad M.Covalent organic frameworks: synthesis, properties and applications-An overview. Polymers (Basel) 2021;13: 970.

[13] Mandal AK, Mahmood J, Baek J. Two-dimensional covalent organic frameworks for optoelectronics and energy storage. ChemNanoMat 2017; 3:373-91.

[14] Li X, Yang C, Sun B, Cai S, Chen Z, Lv Y, et al. Expeditious synthesis of covalent organic frameworks: a review. J Mater Chem A 2020; 8:16045-60.

[15] Geng K, He T, Liu R, Dalapati S, Tan KT, Li Z, et al. Covalent organic frameworks: design, synthesis, and functions. Chem Rev 2020; 120:8814-33.

[16] Lohse MS, Bein T. Covalent organic frameworks: structures, synthesis, and applications. Adv Funct Mater 2018; 28:1705553.

[17] Guan X, Fang Q, Yan Y, Qiu S. Functional regulation and stability engineering of three-dimensional covalent organic frameworks. Acc Chem Res 2022; 55:1912-27.

[18] Zhang T, Zhang G, Chen L. 2D conjugated covalent organic frameworks: defined synthesis and tailor-made functions. Acc Chem Res 2022; 55:795-808.

[19] Cote AP, Benin AI, Ockwig NW, O'Keeffe M, Matzger AJ, Yaghi OM. Porous, crystalline, covalent organic frameworks. Science 2005; 310:1166-70.

[20] Gao C, Bai J, He Y, Zheng Q, Ma W, Lin Z. Post-synthetic modification of phenylboronic acid-functionalized magnetic covalent organic frameworks for specific enrichment of N-linked glycopeptides. ACS Sustainable Chem Eng 2019; 7:18926-34.

[21] Li Y, Chen W, Xing G, Jiang D, Chen L. New synthetic strategies toward covalent organic frameworks. Chem Soc Rev 2020; 49:2852-68.

[22] Lyle SJ, Waller PJ, Yaghi OM. Covalent organic frameworks: organic chemistry extended into two and three dimensions. Trends Chem 2019; 1:172-84.

[23] Zhu Y. Design, synthesis and gas adsorption study of porous organic polymers (POPs) and covalent organic frameworks (COFs) through dynamic covalent chemistry[D]. University of Colorado at Boulder; 2016.

[24] Bagheri AR, Li C, Zhang X, Zhou X, Aramesh N, Zhou H, et al. Recent advances in covalent organic frameworks for cancer diagnosis and therapy. Biomater Sci 2021; 9:5745-61.

[25] Tian J, Lin F, Yu S, Yu J, Tang Q, Li Z. Water-dispersible and soluble porous organic polymers for biomedical applications. Aggregate 2022; 3:e187.

[26] Zhang G, Li X, Liao Q Liu Y, Xi K, Huang W, et al. Water-dispersible PEG-curcumin/amine-functionalized covalent organic framework nanocomposites as smart carriers for in vivo drug delivery. Nat Commun 2018; 9:2785.

[27] Rodríguez-San-Miguel D, Montoro C, Zamora F. Covalent organic framework nanosheets: preparation, properties and applications. Chem Soc Rev 2020; 49:2291-302.

[28] Smith BJ, Hwang N, Chavez AD, Novotney JL, Dichtel WR. Growth rates and water stability of 2D boronate ester covalent organic frameworks. Chem Commun 2015; 51:7532-5.

[29] Shi Y, Yang J, Gao F, Zhang Q. Covalent organic frameworks: recent progress in biomedical applications. ACS Nano 2023; 17:1879-905.

[30] Sun Q, Fu CW, Aguila B, Perman J, Wang S, Huang HY, et al. Pore environment control and enhanced performance of enzymes infiltrated in covalent organic frameworks. J Am Chem Soc 2018; 140:984-92.

[31] Zhang G, Jiang B, Wu C, Liu Y, He Y, Huang X, et al. Thin platelet-like COF nanocomposites for blood brain barrier transport and inhibition of brain metastasis from renal cancer. J Mater Chem B 2020; 8:4475-88.

[32] Sun Q, Aguila B, Perman J, Earl LD, Abney CW, Cheng Y, et al. Postsynthetically modified covalent organic frameworks for efficient and effective mercury removal. J. Am Chem Soc. 2017; 139:2786-93.

[33] Huang N, Zhai L, Coupry DE, Addicoat MA, Okushita K, Nishimura K, et al. Multiple-component covalent organic frameworks. Nat Commun 2016; 7:12325.

[34] Du Y, Yang H, Whiteley JM, Wan S, Jin Y, Lee SH, et al. Ionic covalent organic frameworks with spiroborate linkage. Angewandte Chemie Int Edit 2016; 55:1737-41.

[35] Meng T, Wang X, Jiang S, Chen SR, Zhou S, Zhu Y, et al. Delivery of small-molecule drugs and protein drugs by injectable acid-responsive self-assembled COF hydrogels for combinatorial lung cancer treatment. ACS Appl Mater Interfaces 2023; 15:42354-68.

[36] Nagai A, Guo Z, Feng X, Jin S, Chen X, Ding X, et al. Pore surface engineering in covalent organic frameworks. Nat Commun 2011; 2:536.

[37] Dautzenberg E, Lam M, Li G, de Smet LC. Enhanced surface area and reduced pore collapse of methylated, imine-linked covalent organic frameworks. Nanoscale 2021; 13:19446-52.

[38] Singh N, Kim J, Kim J, Lee K, Zunbul Z, Lee I, et al. Covalent organic framework nanomedicines: biocompatibility for advanced nanocarriers and cancer theranostics applications. Bioactive Mater 2023; 21:358-80.

[39] Li Z, He T, Gong Y, Jiang D. Covalent organic frameworks: pore design and interface engineering. Acc Chem Res 2020; 53:1672-85.

[40] Huang N, Krishna R, Jiang D. Tailor-made pore surface engineering in covalent organic frameworks: systematic functionalization for performance screening. J Am Chem Soc 2015; 137:7079-82.

[41] Deng L, Ding Z, Ye X, Jiang D. Covalent organic frameworks: chemistry of pore interface and wall surface perturbation and impact on functions. Acc Mater Res 2022; 3:879-93.

[42] Chowdhury S, Sharma A, Das PP, Rathi P, Siril PF. Fine-tuning covalent organic frameworks for structure-activity correlation via adsorption and catalytic studies. J Colloid Interface Sci 2024; 665:988-98.

[43] Feriante CH, Jhulki S, Evans AM, Dasari RR, Slicker K, Dichtel WR, et al. Rapid synthesis of high surface area imine-linked 2D covalent organic frameworks by avoiding pore collapse during isolation. Adv Mater 2020; 32:1905776.

[44] Liu X, Huang D, Lai C, Zeng G, Qin L, Wang H, et al. Recent advances in covalent organic frameworks (COFs) as a smart sensing material. Chem Soc Rev 2019; 48:5266-302.

[45] Liu X, Pang H, Liu X, Li Q, Zhang N, Mao L, et al. Orderly porous covalent organic frameworks-based materials: superior adsorbents for pollutants removal from aqueous solutions. Innovation 2021; 2:100076.

[46] Sridhar V, Yildiz E, Rodríguez-Camargo A, Lyu X, Yao L, Wrede P, et al. Designing covalent organic framework-based light-driven microswimmers toward therapeutic applications. Adv Mater 2023; 35:2301126.

[47] Zhang Y, Xu X, Liao Q, Wang Q, Han Q, Chen P, et al. New potential of boron-based COFs: the biocompatible COF-1 for reactive oxygen generation and antimicrobial applications. J Mater Chem B 2022; 10:3285-92.

[48] Mokhtari N, Dinari M, Khosravi Esmaeiltarkhani F. Imine-linked covalent organic frameworks: a biocompatible and pH -dependent carrier for in vitro sustained release of doxorubicin. ACS Omega 2023; 8:25565-73.

[49] Yazdani H, Shahbazi MA. Varma RS. 2D and 3D covalent organic frameworks: cutting-edge applications in biomedical sciences. ACS Appl Bio Mater 2021; 5:40-58.

[50] Guan Q, Zhou L, Li W, Li Y, Dong Y. Covalent organic frameworks (COFs) for cancer therapeutics. Chem: Eur J 2020; 26:5583-91.

[51] He X, Jiang Z, Akakuru OU, Li J, Wu A. Nanoscale covalent organic frameworks: from controlled synthesis to cancer therapy. Chem Comms 2021; 57:12417-35.

[52] Mal A, Ding H, Li M, Li W, Wang C. Covalent organic frameworks with nanopores for biological applications: a review. ACS Appl Nano Mater 2022; 5:13972-84.

[53] Huang C, Zhou S, Chen C, Wang X, Ding R, Xu Y, et al. Biodegradable redox-responsive AIEgen-based covalent organic framework nanocarriers for long-term treatment of myocardial ischemia/reperfusion injury. Small 2022; 18:2205062.

[54] Han Y, Wang S, Cao Y, Singh GP, Loh SI, Cheerlavancha R, et al. Design of biodegradable, climate-specific packaging materials that sense food spoilage and extend shelf life. ACS Nano 2023; 17:8333-44.

[55] Fang Q, Wang J, Gu S, Kaspar RB, Zhuang Z, Zheng J, et al. 3D porous crystalline polyimide covalent organic frameworks for drug delivery. J Am Chem Soc 2015; 137:8352-5.

[56] Kandambeth S, Venkatesh V, Shinde DB, Kumari S, Halder A, Verma S, et al.Self-templated chemically stable hollow spherical covalent organic framework. Nat Commun 2015; 6:1-10.

[57] Bai L, Phua SZ, Lim WQ, Jana A, Luo Z, Tham HP, et al. Nanoscale covalent organic frameworks as smart carriers for drug delivery. Chem Comms 2016; 52:4128-31.

[58] Vyas VS, Vishwakarma M, Moudrakovski I, Haase F, Savasci G, Ochsenfeld C, et al. Exploiting noncovalent interactions in an imine-based covalent organic framework for quercetin delivery. Adv Mater 2016; 28:8749-54.

[59] Mitra S, Sasmal HS, Kundu T, Kandambeth S, Illath K, Díaz Díaz D, et al. Targeted drug delivery in covalent organic nanosheets (CONs) via sequential postsynthetic modification. J Am Chem Soc 2017; 139:4513-20.

[60] Liu S, Hu C, Liu Y, Zhao X, Pang M, Lin J. One-pot synthesis of DOX@covalent organic framework with enhanced chemotherapeutic efficacy. Chem: Eur J 2019; 25:4315-9.

[61] Wang K, Zhao W, Liu H. Cyanine-assisted exfoliation of covalent organic frameworks in nanocomposites for highly efficient chemo-photothermal tumor therapy. ACS Appl Mater Interfaces 2019; 11:39503-12.

[62] Zhao W, Wang K, Zhang L. 3D Hydrazone-functionalized covalent organic frameworks as ph-triggered rotary switches. Small 2021; 17:2102630.

[63] Ploetz E, Engelke H, Lächelt U, Wuttke S. The chemistry of reticular framework nanoparticles: MOF, ZIF, and COF materials. Adv Funct Mater 2020; 30:1909062.

[64] Zhang L, Wang K, Liu H. Nature-inspired construction of MOF@COF nanozyme with active sites in tailored microenvironment and pseudopodia-like surface for enhanced bacterial inhibition. Angew Chem Int Ed 2021; 60:3469-74.

[65] Freund R, Lächelt U, Gruber T, Rühle B, Wuttke S. Multifunctional efficiency: extending the concept of atom economy to functional nanomaterials. ACS Nano 2018; 12:2094-105.

[66] Zhang L, Zhao W, Liu H. Staggered stacking covalent organic frameworks for boosting cancer immunotherapy. Adv Funct Mater 2022; 32:2201542.

[67] Liu H, Schreiber SL, Stockwell BR. Targeting dependency on the GPX4 lipid peroxide repair pathway for cancer therapy. Biochemistry 2018; 57:2059-60.

[68] Guan Q Zhou LL, Dong YB. Ferroptosis in cancer therapeutics: a materials chemistry perspective. J Mater Chem B 2021; 9:8906-36.

[69] Zhou L, Guan Q, Li W, Zhang Z, Li Y, Dong Y. A ferrocene-functionalized covalent organic framework for enhancing chemodynamic therapy via redox dyshomeostasis. Small 2021; 17:2101368.

[70] Zhang C, Wang K, Liu H. A mitochondria-targeting dinuclear Ir-Ru complex as a synergistic photoactivated chemotherapy and photodynamic therapy agent against cisplatin-resistant tumour cells. Chem Commun 2019; 55:12547-50.

[71] Liao C, Liu S. Tuning the physicochemical properties of reticular covalent organic frameworks (COFs) for biomedical applications. J Mater Chem B 2021; 9:6116-28.

[72] Wang X, Liao C, Zhou S. Covalent organic frameworks as a biomacromolecule immobilization platform for biomedical and related applications. Adv Ther 2022; 5:2200053.

[73] Zhou S, Liao C, Wang X. Characteristic synthesis of a covalent organic framework and its application in multifunctional tumor therapy. ACS Appl Bio Mater 2021; 5:59-81.

[74] Chen TT, Yi JT, Zhao YY, Chu X. Biomineralized metal-organic framework nanoparticles enable intracellular delivery and endo-lysosomal release of native active proteins. J Am Chem Soc 2018; 140:9912-20.

[75] Liang J, Ruan J, Njegic B, Rawal A, Scott J, Xu J, et al. Insight into bioactivity of in-situ trapped enzyme-covalent-organic frameworks. Angew Chem Int Ed Engl 2023;62: e202303001.

[76] Di Z, Qi Y, Yu XX, Li HR, Zuo MX, Ren TT, et al. Facile and scale-up syntheses of high-performance enzyme@meso-HOF biocatalysts. Chem Sci 2024; 15:16987-96.

[77] Benyettou F, Kaddour N, Prakasam T, Das G, Sharma SK, Thomas SA, et al. In vivo oral insulin delivery via covalent organic frameworks. Chem Sci 2021; 12:6037-47.

[78] Wang Y, Shahi PK, Xie R. A pH-responsive silica-metal-organic framework hybrid nanoparticle for the delivery of hydrophilic drugs, nucleic acids, and CRISPR-Cas9 genome-editing machineries. J Control Release 2020; 324:194-203.

[79] Zhang G, Ji Y, Li X, Wang X, Song M, Gou H, et al. Polymer-covalent organic frameworks composites for glucose and pH dual-responsive insulin delivery in mice. Adv Healthc Mater 2020; 9(14):e2000221.

[80] Wang Z, Zhang S, Chen Y, Zhang Z, Ma S. Covalent organic frameworks for separation applications. Chem Soc Rev 2020; 49:708-35.

[81] Evans AM, Liu J, Zhou S. Seeded growth of single-crystal two-dimensional covalent organic frameworks. Science 2018; 361:52-7.

[82] Wang H, Liao C, Zhang G. Recent progress in covalent organic framework thin films: fabrications, applications and perspectives. Chem Soc Rev 2019; 48:488-516.

[83] Wu S, Zhao K, Wang J, Liu N, Nie K, Qi L, et al. Recent advances of tanshinone in regulating autophagy for medicinal research. Front Pharmacol 2023; 13:1059360.

[84] Li Q, Qi L, Zhao K, Ke W, Li T, Xia L. Integrative quantitative and qualitative analysis for the quality evaluation and monitoring of Danshen medicines from different sources using HPLC-DAD and NIR combined with chemometrics. Front Plant Sci 2022; 13:932855.

[85] Li Q, Yan X, Zhao K, Li L, Peng S, Luo X, et al. Fast inspection of saffron on the spot based on cloud-connected portable near-infrared technology. Spectrosc Spectral Anal 2020; 40:3029-37.

[86] Sindhwani S, Syed AM, Ngai J, Kingston BR, Maiorino L, Rothschild J, et al. The entry of nanoparticles into solid tumours. Nat Mater 2020; 19:566-75.

[87] Tao W, Kong N, Ji X, Zhang Y, Sharma A, Ouyang J, et al. Emerging two-dimensional monoelemental materials (Xenes) for biomedical applications. Chem Soc Rev 2019; 48:2891-912.

[88] Peña Q Wang A, Zaremba O, Shi Y, Scheeren HW, Metselaar JM, et al. Metallodrugs in cancer nanomedicine. Chem Soc Rev 2022; 51:2544-82.

[89] Gao P, Shen X, Liu X, Chen Y, Pan W, Li N, et al. Nucleic acid-gated covalent organic frameworks for cancer-specific imaging and drug release. Anal Chem 2021; 93:11751-7.

[90] He J, Li C, Ding L, Huang Y, Yin X, Zhang J, et al. Tumor targeting strategies of smart fluorescent nanoparticles and their applications in cancer diagnosis and treatment. Adv Mater 2019; 31:1902409.

[91] Mitra S, Kandambeth S, Biswal BP, Khayum MA, Choudhury CK, Mehta M, et al. Self-exfoliated guanidinium-based ionic covalent organic nanosheets (iCONs). J Am Chem Soc 2016; 138(8):2823-8.

[92] Sun Q, Aguila B, Lan PC, Ma S. Tuning pore heterogeneity in covalent organic frameworks for enhanced enzyme accessibility and resistance against denaturants. Adv Mater 2019; 31:1900008.

[93] Mal A, Mishra RK, Praveen VK, Khayum MA, Banerjee R, Ajayaghosh A. Supramolecular reassembly of self-exfoliated ionic covalent organic nanosheets for label-free detection of double-stranded DNA. Angew Chem 2018; 130:8579-83.

[94] Chen H, Wenqiang C, Linhui F, Sufeng Z, Chen L. Covalent organic frameworks (COFs) materials in enzyme immobilization and mimic enzymes. Prog Chem 2020; 32:895.

[95] Ghosh P, Banerjee P. Drug delivery using biocompatible covalent organic frameworks (COFs) towards a therapeutic approach. Chem Commun 2023; 59:12527-47.

[96] Ghahari A, Raissi H, Farzad F. Design of a new drug delivery platform based on surface functionalization 2D covalent organic frameworks. J Taiwan Inst Chem Eng 2021; 125:15-22.

[97] Feng T, Shi X, Ju T, Long J, Liu Q, Liu M, et al. 3D-/2D-covalent organic framework (COF) bilayered membranes for efficient pharmaceutical purification. J Membrane Sci 2024; 709:123144.

[98] Mehvari F, Ramezanzade V, Asadi P, Singh N, Kim J, Dinari M, et al. A panoramic perspective of recent progress in 2D and 3D covalent organic frameworks for drug delivery: special issue: emerging Investigators. Aggregate 2024; 5(2):e480.

[99] Daugherty M, Daugherty E, Jacob J, Shapiro O, Mollapour M, Bratslavsky G. Renal cell carcinoma and brain metastasis: questioning the dogma of role for cytoreductive nephrectomy. Urologic oncology: seminars and original investigations 2019; 37(3):182e9-e15.

[100] Zhang H, Wang T, Qiu W, Han Y, Sun Q, Zeng J, et al. Monitoring the opening and recovery of the blood-brain barrier with noninvasive molecular imaging by biodegradable ultrasmall Cu2-x Se nanoparticles. Nano Lett 2018; 18:4985-92.

[101] Furtado D, Björnmalm M, Ayton S, Bush AI, Kempe K, Caruso F. Overcoming the blood-brain barrier: the role of nanomaterials in treating neurological diseases. Adv Mater 2018; 30:1801362.

[102] Karaman MW, Herrgard S, Treiber DK, Gallant P, Atteridge CE, Campbell BT, et al. A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol 2008; 26(1):127-32.

[103] Andronescu Ecaterina, and alexandru mihai grumezescu, eds. nanostructures for oral medicine. Amsterdam, Netherlands: Elsevier; 2017.

[104] Ji C, Li J, Mei J, et al. Advanced nanomaterials for the diagnosis and treatment of renal cell carcinoma. Adv NanoBiomed Res 2023; 3(2):2200079.

[105] Pei H, Han C, Bi J, He Z, Guo L. Dihydromyricetin suppresses inflammatory injury in microglial cells to improve neurological behaviors of Alzheimer's disease mice via the TLR4/MD2 signal. Int Immunopharmacol 2023; 118:110037.

[106] Xiong RR, Ling GX, Zhang YQ, Guan JB, Zhang P. Nucleic acid delivery by ionizable nanocarriers for brain disease treatment. Brain-X 2023; 1:e7.

[107] Maleki R, Khedri M, Rezvantalab S, Afsharchi F, Musaie K, Shafiee S, et al. $\beta$-amyloid targeting with two-dimensional covalent organic frameworks: multi-scale in-silico dissection of nano-biointerface. Chembiochem 2021; 22(13):2306-18.

[108] Guan Q, Wang GB, Zhou LL, Li WY, Dong YB. Nanoscale covalent organic frameworks as theranostic platforms for oncotherapy: synthesis, functionalization, and applications. Nanoscale Adv 2020; 2:3656-733.

[109] Kunzelmann K. Getting hands on a drug for Covid-19: inhaled and intranasal niclosamide. Lancet Reg Health Eur 2021; 4:1-2.

[110] Matthay MA, Ware LB, et al. Acute respiratory distress syndrome. Nat Rev Dis Primers 2019; 5:18.

[111] He S, Wu L, Sun H, Wu D, Wang C, Ren X, et al. Antioxidant biodegradable covalent cyclodextrin frameworks as particulate carriers for inhalation therapy against acute lung injury. ACS Appl Mater Interfaces 2022; 14:38421-35.

[112] Zhao K, Qian C, Qi L, Li Q, Zhao C, Zhang J, et al. Modified acid polysaccharide derived from Salvia przewalskii with excellent wound healing and enhanced bioactivity. Int J Biol Macromol 2024; 263(Pt 2):129803.

[113] Zhang H, Liang Y, Zhao H, Qi R, Chen Z, Yuan H, et al. Dual-mode antibacterial conjugated polymer nanoparticles for photothermal and photodynamic therapy. Macromol Biosci 2020; 20:1900301.

[114] Cui Q, Yuan H, Bao X, Ma G, Wu M, Xing C. Synergistic photodynamic and photothermal antibacterial therapy based on a conjugated polymer nanoparticle-doped hydrogel. ACS Appl Bio Mater 2020; 3:4436-44.

[115] Bilici K, Atac N, Muti A, Baylam I, Dogan O, Sennaroglu A, et al. Broad spectrum antibacterial photodynamic and photothermal therapy achieved with indocyanine green loaded SPIONs under near infrared irradiation. Biomater Sci 2020; 8:4616-25.

[116] Ma W, Chen X, Fu L, Zhu J, Fan M, Chen J, et al. Ultra-efficient antibacterial system based on photodynamic therapy and CO gas therapy for synergistic antibacterial and ablation biofilms. ACS Appl Mater Interfaces 2020; 12:22479-91.

[117] Wang Y, Li H, Rasool A, Wang H, Manzoor R, Zhang G. Polymeric nanoparticles (PNPs) for oral delivery of insulin. J Nanobiotechnol 2024; 22:1.

[118] Bagheri E, Ansari L, Abnous K, Taghdisi SM, Charbgoo F, Ramezani M, et al. Silica based hybrid materials for drug delivery and bioimaging. J Control Release 2018;277: 57-76.

[119] Yang Y, Zhou R, Wang Y, Zhang Y, Yu J, Gu Z. Recent advances in oral and transdermal protein delivery systems. Angew Chem 2023; 135:e202214795.

[120] Lu Y, Yu H, Wang L, Shen D, Chen X, Huang Y, et al. Recent advances in the smart insulin delivery systems for the treatment of diabetes. Eur Polym J 2021; 161:110829.

[121] Guan Q, Zhou LL, Li YA, Li WY, Wang S, Song C, et al. Nanoscale covalent organic framework for combinatorial antitumor photodynamic and photothermal therapy. ACS Nano 2019; 13:13304-16.

[122] Li RL, Flanders NC, Evans AM, Ji W, Castano I, Chen LX, et al. Controlled growth of imine-linked two-dimensional covalent organic framework nanoparticles. Chem Sci 2019; 10:3796-801.

[123] Chen Y, Chen X, Yu H, Zhou H, Xu S. Oral microbiota as promising diagnostic biomarkers for gastrointestinal cancer: a systematic review. Onco Targets Ther 2019; 12:11131-44.

[124] Dreyer H, Grischke J, Tiede C, Eberhard J, Schweitzer A, Toikkanen SE, et al. Epidemiology and risk factors of peri-implantitis: a systematic review. J Periodontal Res 2018; 53:657-81.

[125] Wan Y, Xu W, Ren X, Wang Y, Dong B, Wang L. Microporous frameworks as promising platforms for antibacterial strategies against oral diseases. Front Bioeng Biotechnol 2020; 8:628.

[126] Chen Y, Li P, Modica JA, Drout RJ, Farha OK. Acid-resistant mesoporous metal-organic framework toward oral insulin delivery: protein encapsulation, protection, and release. J Am Chem Soc 2018; 140:5678-81.

[127] Jain RK. Transport of molecules in the tumor interstitium: a review. Cancer Res 1987; 47:3039-51.

[128] He X, Yang Y, Li L, Zhang P, Guo H, Liu N, et al. Engineering extracellular matrix to improve drug delivery for cancer therapy. Drug Discov Today 2020; 25:1727-34.

[129] Salavati H, Debbaut C, Pullens P, Ceelen W. Interstitial fluid pressure as an emerging biomarker in solid tumors. Biochim Biophys Acta Rev Cancer 2022; 1877:188792.

[130] Yang Q, Guo N, Zhou Y, Chen J, Wei Q, Han M. The role of tumor-associated macrophages (TAMs) in tumor progression and relevant advance in targeted therapy. Acta Pharm Sin B 2020; 10:2156-70.

[131] Zhao F, Liu H, Dong A, Zhang J. Mathe SDR, Covalent organic frameworks: from materials design to biomedical application. Nanomaterials 2017; 8:15.

[132] Bozzuto G, Molinari A. Liposomes as nanomedical devices. Int J Nanomed 2015; 10:975-99.

[133] Baig N, Kammakakam I, Falath W. Nanomaterials: a review of synthesis methods, properties, recent progress, and challenges. Mater Adv 2021; 2:1821-71.

[134] Sakamaki Y, Ozdemir J, Heidrick Z, Watson O, Shahsavari HR, Fereidoonnezhad M, et al. Metal-organic frameworks and covalent organic frameworks as platforms for photodynamic therapy. Comments Inorg Chem 2018; 38:238-93.

[135] Horcajada P, Serre C, Vallet-Regí M, Sebban M, Taulelle F, Férey G. Metal-organic frameworks as efficient materials for drug delivery. Angew Chem Int Ed 2006; 45:5974-8.

[136] Niu H, Bu H, Zhao J, Zhu Y. Metal-organic frameworks-based nanoplatforms for the theranostic applications of neurological diseases. Small 2023; 19:2206575.

[137] Li X, Yue R, Guan G, Zhang C, Zhou Y, Song G. Recent development of pH -responsive theranostic nanoplatforms for magnetic resonance imaging-guided cancer therapy. Exploration 2023; 3:20220002.

[138] Zhang Y, Sheng J, Zhai F, Wang X, Chen L, Shi C, et al. Pioneering iodine-125-labeled nanoscale covalent organic frameworks for brachytherapy. Bioconjug Chem 2021; 32:755-62.

[139] Ni K, Luo T, Nash GT, Lin W. Nanoscale metal-organic frameworks for cancer immunotherapy. Acc Chem Res 2020; 53:1739-48.

[140] Zhang H, Cao Y, Li w, Zhang S, Song S, Wang Y, et al. Ferroptosis-induced immunomodulation with biometabolic MOF@COF nanovaccine for self-boosting anti-tumor immunotherapy. Chem Eng J 2024; 493:152675.