Metal-organic frameworks in pharmaceutical research

Abstract

Metal-organic frameworks (MOFs) have emerged as a highly versatile class of porous materials with significant potential to advance pharmaceutical research. This review provides a comprehensive overview of the current landscape of MOFs, encompassing their synthesis strategies, characterization methodologies, and diverse biomedical applications. We detail various synthesis approaches (e.g., hydrothermal, electrochemical, microwave) and essential characterization techniques (e.g., X-ray diffraction (XRD), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) surface area analysis) that are critical for developing well-defined MOF structures. The review highlights the key advantages of MOFs in drug delivery, including their exceptional drug loading capacity, good biocompatibility, and capabilities for sustained, controlled, and targeted release. Their applications in improving drug solubility and stability, enabling pulmonary delivery, and functioning in biosensing, antimicrobial therapy, and nucleic acid delivery are also extensively discussed. Furthermore, we explore the utility of MOFs in drug structure analysis and the development of advanced functional systems, such as stimuli-responsive and self-propelled MOFs. Despite promising preclinical progress, challenges related to scalability, reproducibility, and long-term biosafety remain to be addressed for successful clinical translation. This work aims to bridge the gap between MOF materials science and pharmaceutical applications, offering valuable insights for the rational design of next-generation drug delivery systems and therapeutic platforms.

Keywords

Metal-organic framework / Drugs / Drug delivery system / Structural analysis

CRediT authorship contribution statement

Zimeng Tao: Writing - original draft, Formal analysis, Conceptualization. Kun Hu: Data curation, Conceptualization. Baoxi Zhang: Formal analysis, Data curation. Shiying Yang: Formal analysis, Data curation. Dezhi Yang: Writing - review & editing, Methodology, Funding acquisition. Zhehui Zhao: Methodology, Conceptualization. Li Zhang: Methodology. Yang Lu: Methodology, Funding acquisition.

Ethics approval

Not applicable.

Declaration of generative AI in scientific writing

During the preparation of this work, the authors used DeepSeek to improve language and readability. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.

Funding information

This research was funded by the National Natural Science Foundation of China [Grant No. 22278443] and the CAMS Innovation Fund for Medical Sciences [Grant No. 2022-I2M-1-015].

Data availability

Not applicable.

Declaration of competing interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

The graphical abstract was created using WPS Office software. Specifically, the MOF structure depicted in the graphical abstract was generated using the OneKeyTools plugin within WPS.

References

[1] D.K. Bučar, G.S. Papaefstathiou, T.D. Hamilton, Q.L. Chu, I.G. Georgiev, L. R. MacGillivray, Template-controlled reactivity in the organic solid state by principles of coordination-driven self-assembly, Eur. J. Inorg. Chem. 2007 (29) (2007) 4559-4568, https://doi.org/10.1002/ejic.200700442.

[2] B. Li, H.M. Wen, Y. Cui, W. Zhou, G. Qian, B. Chen, Emerging multifunctional metal-organic framework materials, Adv. Mater. (Deerfield Beach, Fla.) 28 (40) (2016) 8819-8860, https://doi.org/10.1002/adma.201601133.

[3] E.R. Parnham, R.E. Morris, Ionothermal synthesis of zeolites, metal-organic frameworks, and inorganic-organic hybrids, Accounts Chem. Res. 40 (10) (2007) 1005-1013, https://doi.org/10.1021/ar700025k.

[4] O.M. Yaghi, G. Li, H. Li, Selective binding and removal of guests in a microporous metal-organic framework, Nature 378 (6558) (1995) 703-706, https://doi.org/10.1038/378703a0.

[5] S. Kitagawa, S. Kawata, Y. Nozaka, M. Munakata, Synthesis and crystal structures of novel copper (I) co-ordination polymers and a hexacopper (I) cluster of quinoline-2-thione, J. Chem. Soc., Dalton Trans. (9) (1993) 1399-1404, https://doi.org/10.1039/DT9930001399.

[6] S. Kitagawa, S. Matsuyama, M. Munakata, T. Emori, Synthesis and crystal structures of novel one-dimensional polymers, $\left[\left\{\mathrm{M}\right(\text{ }\text{bpen}\text{ })\mathrm{X}{\}}_{\mathrm{\infty }}\right]$[M=Cu^I,X=PF₆^-; M=Ag^I,X=ClO₄^-; bpen=trans-1,2-bis(2-pyridyl)ethylene] and [{$\mathrm{C}\mathrm{u}\left(\mathrm{b}\mathrm{p}\mathrm{e}\mathrm{n}\right)\left(\mathrm{C}\mathrm{O}\right)\left.{\left.\left({\mathrm{C}\mathrm{H}}_{3}\mathrm{C}\mathrm{N}\right)\left({\mathrm{P}\mathrm{F}}_{6}\right)\right\}}_{\mathrm{\infty }}\right]$, J. Chem. Soc., Dalton Trans. 11 (1991) 2869-2874, https://doi.org/10.1039/DT9910002869.

[7] H. Li, M. Eddaoudi, M. O'Keeffe, O.M. Yaghi, Design and synthesis of an exceptionally stable and highly porous metal-organic framework, Nature 402 (6759) (1999) 276-279, https://doi.org/10.1038/46248.

[8] G. Férey, C. Serre, C. Mellot-Draznieks, F. Millange, S. Surblé, J. Dutour, I. Margiolaki, A hybrid solid with giant pores prepared by a combination of targeted chemistry, simulation, and powder diffraction, Angew. Chem. Int. Ed. 116 (46) (2004) 6456-6461, https://doi.org/10.1002/anie.200460592.

[9] K.S. Park, Z. Ni, A.P. Côté, J.Y. Choi, R. Huang, F.J. Uribe-Romo, H.K. Chae, M. O'Keeffe, O.M. Yaghi, Exceptional chemical and thermal stability of zeolitic imidazolate frameworks, Proc. Natl. Acad. Sci. U. S. A 103 (27) (2006) 10186-10191, https://doi.org/10.1073/pnas.0602439103.

[10] J.H. Cavka, S. Jakobsen, U. Olsbye, N. Guillou, C. Lamberti, S. Bordiga, K. P. Lillerud, A new zirconium inorganic building brick forming metal organic frameworks with exceptional stability, J. Am. Chem. Soc. 130 (42) (2008) 13850-13851, https://doi.org/10.1021/ja8057953.

[11] S. Jia, P. Lin, Y. Li, Y. Teng, J. Wang, T. Yang, L. Li, C. Wang, X. Li, Flexible UiO67 (Zr)@cyclodextrin-based nanofiber membrane for efficient removal of ibuprofen, Separ. Purif. Technol. 333 (2024) 125850, https://doi.org/10.1016/j.seppur.2023.125850.

[12] S. Alvandi, M. Hosseinifard, M. Bababmoradi, Enhancement of Pb (ii) adsorptive removal by incorporation of UiO-66-COOH into the magnetic graphitic carbon nitride nanosheets, Royal Soc. Chem. 14 (13) (2024) 8990-9002, https://doi.org/10.1039/d4ra00364k.

[13] D. Ning, Q. Liu, Q. Wang, X.-M. Du, Y. Li, W.-J. Ruan, Pyrene-based MOFs as fluorescent sensors for PAHs: an energetic pathway of the backbone structure effect on response, Dalton Trans. 48 (17) (2019) 5705-5712, https://doi.org/10.1039/c9dt00492k.

[14] P. Deria, J.E. Mondloch, E. Tylianakis, P. Ghosh, W. Bury, R.Q. Snurr, J.T. Hupp, O.K. Farha, Perfluoroalkane functionalization of NU-1000 via solvent-assisted ligand incorporation: synthesis and CO₂ adsorption studies, J. Am. Chem. Soc. 135 (45) (2013) 16801-16804, https://doi.org/10.1021/ja408959g.

[15] P.K. Verma, L. Huelsenbeck, A.W. Nichols, T. Islamoglu, H. Heinrich, C. W. Machan, G. Giri, Controlling polymorphism and orientation of NU-901/NU1000 metal-organic framework thin films, Chem. Mater. 32 (24) (2020) 10556-10565, https://doi.org/10.1021/acs.chemmater.0c03539.

[16] M. Dan-Hardi, C. Serre, T. Frot, L. Rozes, G. Maurin, C. Sanchez, G. Férey, A new photoactive crystalline highly porous titanium (IV) dicarboxylate, J. Am. Chem. Soc. 131 (31) (2009) 10857-10859, https://doi.org/10.1021/ja903726m.

[17] P. Horcajada, S. Surblé, C. Serre, D.-Y. Hong, Y.-K. Seo, J.-S. Chang, J.M. Grenèche, I. Margiolaki, G. Ferey, Synthesis and catalytic properties of MIL100 (Fe), an iron (III) carboxylate with large pores, Chem. Commun. (27) (2007) 2820-2822, https://doi.org/10.1039/b704325b.

[18] L.L. Shen, C. Yong, Y. Xu, P. Wu, G.R. Zhang, D. Mei, Recent progress in ZIFDerived carbons for enhanced oxygen reduction reaction electrocatalysis, ChemCatChem 16 (9) (2024) e202301379, https://doi.org/10.1002/cctc.202301379.

[19] G. Zhong, D. Liu, J. Zhang, The application of ZIF-67 and its derivatives: adsorption, separation, electrochemistry and catalysts, J. Mater. Chem. A 6 (5) (2018) 1887-1899, https://doi.org/10.1039/c7ta08268a.

[20] C.-C. Wang, Y.-S. Ho, Research trend of metal-organic frameworks: a bibliometric analysis, Scientometrics 109 (2016) 481-513, https://doi.org/10.1007/s11192-016-1986-2.

[21] D. Chen, J. Zhao, P. Zhang, S. Dai, Mechanochemical synthesis of metal-organic frameworks, Encyclopedia Inorg. Bioinorgan. Chem. 162 (2019) 59-64, https://doi.org/10.1002/9781119951438.eibc2202.

[22] S. Yong-Jiao, W. Shi-Zhen, Z. Wen-Lei, W. Wen-Da, Z. Wen-Dong, H. Jie, Preparation of zinc cobalt composite microstructures derivedfrom metal-organicframwork and gas-sensingproperties of cyclohexanone, Acta Phys. Sin. 71 (10) (2022) 100701, https://doi.org/10.7498/aps.71.20212114.

[23] Y.-R. Lee, J. Kim, W.-S. Ahn, Synthesis of metal-organic frameworks: a mini review, Kor. J. Chem. Eng. 30 (2013) 1667-1680, https://doi.org/10.1007/s11814-013-0140-6.

[24] A. Martinez Joaristi, J. Juan-Alcañiz, P. Serra-Crespo, F. Kapteijn, J. Gascon, Electrochemical synthesis of some archetypical Zn²⁺,Cu²⁺, and Al³⁺ metal organic frameworks, Cryst. Growth Des. 12 (7) (2012) 3489-3498, https://doi.org/10.1021/cg300552w.

[25] S.-E. Park, J.-S. Chang, Y.K. Hwang, D.S. Kim, S.H. Jhung, J.S. Hwang, Supramolecular interactions and morphology control in microwave synthesis of nanoporous materials, Catal. Surv. Asia 8 (2) (2004) 91-110, https://doi.org/10.1023/b:cats.0000026990.25778.a8.

[26] S.H. Jhung, J.-S. Chang, J.S. Hwang, S.-E. Park, Selective formation of SAPO-5 and SAPO-34 molecular sieves with microwave irradiation and hydrothermal heating, Microporous Mesoporous Mater. 64 (1-3) (2003) 33-39, https://doi.org/10.1016/S1387-1811(03)00501-8.

[27] S.H. Jhung, J.-H. Lee, J.W. Yoon, J.-S. Hwang, S.-E. Park, J.-S. Chang, Selective crystallization of CoAPO-34 and VAPO-5 molecular sieves under microwave irradiation in an alkaline or neutral condition, Microporous Mesoporous Mater. 80 (1-3) (2005) 147-152, https://doi.org/10.1016/j.micromeso.2004.11.019.

[28] K.-K. Kang, C.-H. Park, W.-S. Ahn, Microwave preparation of a titaniumsubstituted mesoporous molecular sieve, Chem. Mater. 59 (1999) 45-49, https://doi.org/10.1021/cm000748g.

[29] S.H. Jhung, J.-S. Chang, Y.K. Hwang, S.-E. Park, Crystal morphology control of AFI type molecular sieves with microwave irradiation, J. Mater. Chem. 14 (2) (2004) 280-285, https://doi.org/10.1039/b309142b.

[30] S.-H. Jhung, J.-H. Lee, J.-S. Chang, Microwave synthesis of a nanoporous hybrid material, chromium trimesate, Bull. Kor. Chem. Soc. 26 (6) (2005) 880-881, https://doi.org/10.5012/bkcs.2005.26.6.880.

[31] K.M. Taylor-Pashow, J. Della Rocca, Z. Xie, S. Tran, W. Lin, Postsynthetic modifications of iron-carboxylate nanoscale metal-organic frameworks for imaging and drug delivery, J. Am. Chem. Soc. 131 (40) (2009) 14261-14263, https://doi.org/10.1021/ja906198y.

[32] Z. Ni, R.I. Masel, Rapid production of metal-organic frameworks via microwaveassisted solvothermal synthesis, J. Am. Chem. Soc. 128 (38) (2006) 12394-12395, https://doi.org/10.1021/ja0635231.

[33] Y.-K. Seo, G. Hundal, I.T. Jang, Y.K. Hwang, C.-H. Jun, J.-S. Chang, Microwave synthesis of hybrid inorganic-organic materials including porous Cu₃(BTC)2 from Cu (II)-trimesate mixture, Microporous Mesoporous Mater. 119 (1-3) (2009) 331-337, https://doi.org/10.1016/j.micromeso.2008.10.035.

[34] J.-H. Park, S.-H. Park, S.-H. Jhung, Microwave-syntheses of zeolitic imidazolate framework material, ZIF-8, J. Kor. Chem. Soc. 53 (5) (2009) 553-559, https://doi.org/10.5012/jkcs.2009.53.5.553.

[35] K.S. Suslick, S.-B. Choe, A.A. Cichowlas, M.W. Grinstaff, Sonochemical synthesis of amorphous iron, Nature 353 (6343) (1991) 414-416, https://doi.org/10.1038/353414a0.

[36] A. Gedanken, Using sonochemistry for the fabrication of nanomaterials, Ultrason. Sonochem. 11 (2) (2004) 47-55, https://doi.org/10.1016/j.ultsonch.2004.01.037.

[37] J.K. Won-Jin Son, Jaheon Kim, Wha-Seung Ahn, Sonochemical synthesis of MOF5, Chem. Commun. (2008) 6336-6338, https://doi.org/10.1039/b814740j.

[38] H.-Y. Cho, J. Kim, S.-N. Kim, W.-S. Ahn, High yield 1-L scale synthesis of ZIF-8 via a sonochemical route, Microporous Mesoporous Mater. 169 (2013) 180-184, https://doi.org/10.1016/j.micromeso.2012.11.012.

[39] J.F. Fernandez-Bertran, Mechanochemistry: an overview, Pure Appl. Chem. 71 (4) (1999) 581-586, https://doi.org/10.1351/pac199971040581.

[40] S.B. Norbert Stock, Synthesis of metal-organic frameworks (MOFs): routes to various MOF topologies, morphologies, and composites, Chem. Rev. 112 (2) (2012) 933-969, https://doi.org/10.1021/cr200304e.

[41] A.L. Garay, A. Pichon, S.L. James, Solvent-free synthesis of metal complexes, Chem. Soc. Rev. 36 (6) (2007) 846-855, https://doi.org/10.1039/b600363j.

[42] G.-W. Wang, Mechanochemical organic synthesis, Chem. Soc. Rev. 42 (18) (2013) 7668-7700, https://doi.org/10.1039/c3cs35526h.

[43] K. Kubota, Y. Pang, A. Miura, H. Ito, Redox reactions of small organic molecules using ball milling and piezoelectric materials, Science 366 (6472) (2019) 1500-1504, https://doi.org/10.1126/science.aay8224.

[44] W. Yuan, J. O'Connor, S.L. James, Mechanochemical synthesis of homo-and hetero-rare-earth (III) metal-organic frameworks by ball milling, CrystEngComm 12 (11) (2010) 3515-3517, https://doi.org/10.1039/c0ce00216j.

[45] A. Pichon, S.L. James, An array-based study of reactivity under solvent-free mechanochemical conditions-insights and trends, CrystEngComm 10 (12) (2008) 1839-1847, https://doi.org/10.1039/b810857a.

[46] P.J. Beldon, L. Fábián, R.S. Stein, A. Thirumurugan, A.K. Cheetham, T. Friščić, Rapid room-temperature synthesis of zeolitic imidazolate frameworks by using mechanochemistry, Angew. Chem. Int. Ed. 49 (50) (2010) 9640-9643, https://doi.org/10.1002/anie.201005547.

[47] H. Nabipour, B. Soltani, N. Ahmadi Nasab, Gentamicin loaded Zn₂ (bdc)₂(dabco) frameworks as efficient materials for drug delivery and antibacterial activity, J. Inorg. Organomet. Polym. Mater. 28 (2018) 1206-1213, https://doi.org/10.1007/s10904-018-0781-3.

[48] Y. Bao-Chun, J. Yao-Dong, Q. Xue-Juan, C. Zhi-Liang, R. Fei, Loaded and in vitro drug release of anticancer drugs in porous metal-organic frameworks, Chem. J. Chin. Univ. 33 (1) (2012) 26-31, https://doi.org/10.3969/j.issn.02510790.2012.01.004.

[49] X. Chen, T. Guo, K. Zhang, J. Chen, C. Wang, X. Ren, Q. Wang, Y. Yang, C. Liu, W. Tan, Simultaneous improvement to solubility and bioavailability of active natural compound isosteviol using cyclodextrin metal-organic frameworks, Acta Pharm. Sin. B 11 (9) (2021) 2914-2923, https://doi.org/10.1016/j.apsb.2021.04.018.

[50] Y. Liu, P. Zhou, Z. Cao, W. Liang, J. Yan, H. Xu, L. Wu, L. Sun, L. Gong, C. Peng, Simultaneous solubilization and extended release of insoluble drug as payload in highly soluble particles of γ-cyclodextrin metal-organic frameworks, Int. J. Pharm. 619 (2022) 121685, https://doi.org/10.1016/j.ijpharm.2022.121685.

[51] Y. Yang, F. Xia, Y. Yang, B. Gong, A. Xie, Y. Shen, M. Zhu, Litchi-like Fe₃O₄@Fe- MOF capped with HAp gatekeepers for pH -triggered drug release and anticancer effect, J. Mater. Chem. B 5 (43) (2017) 8600-8606, https://doi.org/10.1039/C7TB01680H.

[52] H. Zhang, W. Jiang, R. Liu, J. Zhang, D. Zhang, Z. Li, Y. Luan, Rational design of metal organic framework nanocarrier-based codelivery system of doxorubicin hydrochloride/verapamil hydrochloride for overcoming multidrug resistance with efficient targeted cancer therapy, ACS Appl. Mater. Interfaces 9 (23) (2017) 19687-19697, https://doi.org/10.1021/acsami.7b05142.

[53] L. Shang, X.-L. Chen, L. Liu, M. Cai, R.-K. Yan, H.-L. Cui, H. Yang, J.-J. Wang, Catalytic performance of MOFs containing trinuclear lanthanides clusters in the cycladdition reaction of CO₂ and epoxide, J. CO₂ Util. 65 (2022) 102235, https://doi.org/10.1016/j.jcou.2022.102235.

[54] F.-M. Zhang, H. Dong, X. Zhang, X.-J. Sun, M. Liu, D.-D. Yang, X. Liu, J.-Z. Wei, Postsynthetic modification of ZIF-90 for potential targeted codelivery of two anticancer drugs, ACS Appl. Mater. Interfaces 9 (32) (2017) 27332-27337, https://doi.org/10.1021/acsami.7b08451.

[55] J.Y. Tse, K. Kadota, T. Nakajima, H. Uchiyama, S. Tanaka, Y. Tozuka, Crystalline rearranged CD-MOF particles obtained via spray-drying synthesis applied to inhalable formulations with high drug loading, Cryst. Growth Des. 22 (2) (2021) 1143-1154, https://doi.org/10.1021/acs.cgd.1c01091.

[56] P.-z. Duan, X.-b. Jia, X. Hou, R. Xia, Y. Guo, X.-f. Zhang, Characterization and adsorption properties of magnetic AL-MOF composite for fluoride, Res. Environ. Sci. 34 (5) (2021) 1139-1147, https://doi.org/10.13198/j.issn.10016929.2020.10.25.

[57] C. Shi, M. Wan, Z. Hou, X. Qian, H. Che, Y. Qin, J. Jing, J. Li, F. Ren, B. Yu, CoMOF@MXene hybrids flame retardants for enhancing the fire safety of thermoplastic polyurethanes, Polym. Degrad. Stabil. 204 (2022) 110119, https://doi.org/10.1016/j.polymdegradstab.2022.110119.

[58] Y. Hassanpouraghdam, M. Pooresmaeil, H. Namazi, In-vitro evaluation of the 5fluorouracil loaded GQDs@Bio-MOF capped with starch biopolymer for improved colon-specific delivery, Int. J. Biol. Macromol. 221 (2022) 256-267, https://doi.org/10.1016/j.ijbiomac.2022.08.167.

[59] C. Guo, Y. Lian, C. Huang, Z. Chen, Sustained-release system based on BTA@MOF-5 for self-healing coating application, Colloids Surf. A Physicochem. Eng. Asp. 654 (2022) 130139, https://doi.org/10.1016/j.colsurfa.2022.130139.

[60] Y. Zhou, M. Zhang, C. Wang, X. Ren, T. Guo, Z. Cao, J. Zhang, L. Sun, L. Wu, Solidification of volatile D-Limonene by cyclodextrin metal-organic framework for pulmonary delivery via dry powder inhalers: in vitro and in vivo evaluation, Int. J. Pharm. 606 (2021) 120825, https://doi.org/10.1016/j.ijpharm.2021.120825.

[61] K.I. Hadjiivanov, D.A. Panayotov, M.Y. Mihaylov, E.Z. Ivanova, K.K. Chakarova, S.M. Andonova, N.L. Drenchev, Power of infrared and Raman spectroscopies to characterize metal-organic frameworks and investigate their interaction with guest molecules, Chem. Rev. 121 (3) (2020) 1286-1424, https://doi.org/10.1021/acs.chemrev.0c00487.

[62] H. Hu, K. Zhang, G. Yan, L. Shi, B. Jia, H. Huang, Y. Zhang, X. Sun, T. Ma, Precisely decorating CdS on Zr-MOFs through pore functionalization strategy: a highly efficient photocatalyst for H₂ production, Chin. J. Catal. 43 (9) (2022) 2332-2341, https://doi.org/10.1016/S1872-2067(21)63949-9.

[63] K. Tabatabaeian, M. Simayee, A. Fallah-Shojaie, F. Mashayekhi, N-doped carbon nanodots@UiO-66- NH₂ as novel nanoparticles for releasing of the bioactive drug, rosmarinic acid and fluorescence imaging, Daru 27 (2019) 307-315, https://doi.org/10.1007/s40199-019-00276-1.

[64] X. Dong, C. Xin, L. Wang, H. Gong, Y. Chen, The role of metal nodes on Rh coordinated MOFs for Hydroformylation of n -butene, Soc. Sci. Res. Netw. 645 (2022) 118848, https://doi.org/10.2139/ssrn.4122443.

[65] J. Jiang, H. Furukawa, Y.-B. Zhang, O.M. Yaghi, High methane storage working capacity in metal-organic frameworks with acrylate links, J. Am. Chem. Soc. 138 (32) (2016) 10244-10251, https://doi.org/10.1021/jacs.6b05261.

[66] J. Della Rocca, D. Liu, W. Lin, Nanoscale metal-organic frameworks for biomedical imaging and drug delivery, Accounts Chem. Res. 44 (10) (2011) 957-968, https://doi.org/10.1021/ar200028a.

[67] H.-C. Zhou, J.R. Long, O.M. Yaghi, Introduction to metal-organic frameworks, Chem. Rev. 112 (2) (2012) 673-674, https://doi.org/10.1021/cr300014x.

[68] J.W. Osterrieth, D. Fairen-Jimenez, Metal-organic framework composites for theragnostics and drug delivery applications, Biotechnol. J. 16 (2) (2021) 2000005, https://doi.org/10.1002/biot.202000005.

[69] L. Bingtai, K. Bangguo, J. Yongjie, B. Pan, Y. Lanning, Anti-tumor drug delivery and tumor therapy based on metal-organic frameworks, Cancer Res. Prevention Treatment 49 (8) (2022) 832-837, https://doi.org/10.3971/j.issn.10008578.2022.21.1457.

[70] Y. Ding, Recent advances of metal-organic frameworks applied in biomedicine, Colloids Surf. B Biointerfaces (2023) 1511-1519, https://doi.org/10.1016/j.colsurfb.2023.113266.

[71] J. Yu, Z. Lin, W. Cao, J. Zhang, Y. Wei, Y. Gao, S. Qian, Research progress of biometal organic frameworks in drug delivery system, J. China Pharm. Univ. (2023) 23-33, https://doi.org/10.11665/j.issn.1000-5048.20221111003.

[72] X.-w. Liao, Y. Liu, C. Wang, Recent progress in nanoscale MOFs for bio- logical imaging of tumors and tumor markers, J. Instrum. Anal. 41 (4) (2022) 476-485, https://doi.org/10.19969/j.fxcsxb.21120704.

[73] J. Della Rocca, D. Liu, W. Lin, Nanoscale metal-organic frameworks for biomedical imaging and drug delivery, Accounts Chem. Res. 44 (10) (2011) 957-968, https://doi.org/10.1021/ar200040w.

[74] Z. Xue, M. Zhu, Y. Dong, T. Feng, Z. Chen, Y. Feng, Z. Shan, J. Xu, S. Meng, An integrated targeting drug delivery system based on the hybridization of graphdiyne and MOFs for visualized cancer therapy, Nanoscale 11 (24) (2019) 11709-11718, https://doi.org/10.1039/c9nr02017a.

[75] C. Orellana-Tavra, E.F. Baxter, T. Tian, T.D. Bennett, N.K. Slater, A.K. Cheetham, D. Fairen-Jimenez, Amorphous metal-organic frameworks for drug delivery, Chem. Commun. 51 (73) (2015) 13878-13881, https://doi.org/10.1039/c5cc05237h.

[76] H. Zheng, Y. Zhang, L. Liu, W. Wan, P. Guo, A.M. Nyström, X. Zou, One-pot synthesis of metal-organic frameworks with encapsulated target molecules and their applications for controlled drug delivery, J. Am. Chem. Soc. 138 (3) (2016) 962-968, https://doi.org/10.1021/jacs.5b11720.

[77] P.Z. Moghadam, T. Islamoglu, S. Goswami, J. Exley, M. Fantham, C.F. Kaminski, R.Q. Snurr, O.K. Farha, D. Fairen-Jimenez, Computer-aided discovery of a metal-organic framework with superior oxygen uptake, Nat. Commun. 9 (1) (2018) 1378, https://doi.org/10.1038/s41467-018-03892-8.

[78] S.E. Miller, M.H. Teplensky, P.Z. Moghadam, D. Fairen-Jimenez, Metal-organic frameworks as biosensors for luminescence-based detection and imaging, Interface Focus 6 (4) (2016) 20160027, https://doi.org/10.1098/rsfs.2016.0027.

[79] L.E. Kreno, K. Leong, O.K. Farha, M. Allendorf, R.P. Van Duyne, J.T. Hupp, Metalorganic framework materials as chemical sensors, Chem. Rev. 112 (2) (2012) 1105-1125, https://doi.org/10.1021/cr200324t.

[80] X. Wang, Z. Niu, A.M. Al-Enizi, A. Nafady, Y. Wu, B. Aguila, G. Verma, L. Wojtas, Y.-S. Chen, Z. Li, Pore environment engineering in metal-organic frameworks for efficient ethane/ethylene separation, J. Mater. Chem. A 7 (22) (2019) 13585-13590, https://doi.org/10.1039/c9ta02822f.

[81] X. Jia, J.L. Dixon, M. Zeller, J. Schrier, A.J. Norquist, Templated vanadium tellurites: identifying the effects of low density attractions on inorganic layer topology, J. Solid State Chem. 273 (2019) 158-165, https://doi.org/10.1016/j.jssc.2019.02.030.

[82] X. Wu, L. Peng, S. Xiang, W. Cai, Computational design of tetrazolate-based metal-organic frameworks for CH₄ storage, Phys. Chem. Chem. Phys. 20 (48) (2018) 30150-30158, https://doi.org/10.1039/c8cp05724a.

[83] H. Li, K. Wang, Y. Sun, C.T. Lollar, J. Li, H.-C. Zhou, Recent advances in gas storage and separation using metal-organic frameworks, Mater. Today 21 (2) (2018) 108-121, https://doi.org/10.1016/j.mattod.2017.07.006.

[84] J.J. Calvin, M. Asplund, Z. Akimbekov, G. Ayoub, A.D. Katsenis, A. Navrotsky, T. Friščić, B.F. Woodfield, Heat capacity and thermodynamic functions of crystalline and amorphous forms of the metal organic framework zinc 2-ethylimidazolate, Zn (EtIm)₂, J. Chem. Thermodyn. 116 (2018) 341-351, https://doi.org/10.1016/j.jct.2017.11.005.

[85] H. Furukawa, K.E. Cordova, M. O'Keeffe, O.M. Yaghi, The chemistry and applications of metal-organic frameworks, Science 341 (6149) (2013) 1230444, https://doi.org/10.1126/science.1230444.

[86] D. Farrusseng, Metal-Organic Frameworks: Applications from Catalysis to Gas Storage, John Wiley & Sons, 2011, https://doi.org/10.1002/9783527635856.

[87] G. Yang, W. Suqing, W. Zhaohui, Application progress of metal-organic frameworks in tumors therapy, Cancer Res. Prevention Treatment 49 (5) (2022) 472-477, https://doi.org/10.3971/j.issn.1000-8578.2022.21.1158.

[88] Y. Zhou, B. Niu, B. Wu, S. Luo, J. Fu, Y. Zhao, G. Quan, X. Pan, C. Wu, A homogenous nanoporous pulmonary drug delivery system based on metalorganic frameworks with fine aerosolization performance and good compatibility, Acta Pharm. Sin. B 10 (12) (2020) 2404-2416, https://doi.org/10.1016/j.apsb.2020.07.018.

[89] P. Horcajada, C. Serre, M. Vallet-Regí, M. Sebban, F. Taulelle, G. Férey, Metal-organic frameworks as efficient materials for drug delivery, Angew. Chem. Int. Ed. 45 (36) (2006) 5974-5978, https://doi.org/10.1002/anie.200601878.

[90] O.K. Farha, I. Eryazici, N.C. Jeong, B.G. Hauser, C.E. Wilmer, A.A. Sarjeant, R. Q. Snurr, S.T. Nguyen, A.O.z.r. Yazaydın, J.T. Hupp, Metal-organic framework materials with ultrahigh surface areas: is the sky the limit? J. Am. Chem. Soc. 134 (36) (2012) 15016-15021, https://doi.org/10.1021/ja3055639.

[91] Y. Yang, F. Xia, Y. Yang, B. Gong, A. Xie, Y. Shen, M. Zhu, Litchi-like Fe₃O₄@Fe- MOF capped with HAp gatekeepers for pH -triggered drug release and anticancer effect, J. Mater. Chem. B 5 (2017) 8600-8606, https://doi.org/10.1039/c7tb01680h.

[92] H. Zhang, W. Jiang, R. Liu, J. Zhang, D. Zhang, Z. Li, Y. Luan, Rational design of metal organic framework nanocarrier-based codelivery System of Doxorubicin Hydrochloride/Verapamil hydrochloride for overcoming multidrug resistance with efficient targeted cancer therapy, ACS Appl. Mater. Interfaces 9 (23) (2017) 19687-19697, https://doi.org/10.1021/acsami.7b05142.

[93] K. Jiang, W. Ni, X. Cao, L. Zhang, S. Lin, A nanosized anionic MOF with rich thiadiazole groups for controlled oral drug delivery, Mater. Today Bio 13 (2021) 100180, https://doi.org/10.1016/j.mtbio.2021.100180.

[94] X. Chen, Z. Shi, R. Tong, S. Ding, X. Wang, J. Wu, Q. Lei, W. Fang, Derivative of epigallocatechin-3-gallatea encapsulated in ZIF-8 with polyethylene glycol-folic acid modification for target and pH -responsive drug release in anticancer research, ACS Biomater. Sci. Eng. 4 (12) (2018) 4183-4192, https://doi.org/10.1021/acsbiomaterials.8b00840.

[95] Y. Zhou, Y. Zhao, B. Niu, Q. Luo, Y. Zhang, G. Quan, X. Pan, C. Wu, Cyclodextrinbased metal-organic frameworks for pulmonary delivery of curcumin with improved solubility and fine aerodynamic performance, Int. J. Pharm. 588 (2020) 119777, https://doi.org/10.1016/j.ijpharm.2020.119777.

[96] V. Veguilla, K. Hancock, J. Schiffer, P. Gargiullo, X. Lu, D. Aranio, A. Branch, L. Dong, C. Holiday, F. Liu, Sensitivity and specificity of serologic assays for detection of human infection with 2009pandemic H₁ N₁ virus in US populations, Clin. Vaccine Immunol. 49 (6) (2011) 2210-2215, https://doi.org/10.1128/CVI.00294-10.

[97] M. Lu, Q. Liu, X. Wang, J. Zhang, X. Zhang, D. Shi, J. Liu, H. Shi, J. Chen, L. Feng, Development of an indirect ELISA for detecting porcine deltacoronavirus IgA antibodies, Arch. Virol. 165 (2020) 845-851, https://doi.org/10.1007/s00705-020-04541-6.

[98] R. Dhumpa, K.J. Handberg, P.H. Jørgensen, S. Yi, A. Wolff, D.D. Bang, Rapid detection of avian influenza virus in chicken fecal samples by immunomagnetic capture reverse transcriptase-polymerase chain reaction assay, Diagn. Microbiol. Infect. Dis. 69 (3) (2011) 258-265, https://doi.org/10.1016/j.diagmicrobio.2010.09.022.

[99] W. Zhang, D.H. Evans, Detection and identification of human influenza viruses by the polymerase chain reaction, J. Virol. Methods 33 (1-2) (1991) 165-189, https://doi.org/10.1016/0166-0934(91)90017-t.

[100] K. Chattopadhyay, M. Mandal, D.K. Maiti, Smart metal-organic frameworks for biotechnological applications: a mini-review, ACS Appl. Bio Mater. 4 (12) (2021) 8159-8171, https://doi.org/10.1021/acsabm.1c00982.

[101] X. Zhu, H. Zheng, X. Wei, Z. Lin, L. Guo, B. Qiu, G. Chen, Metal-organic framework (MOF): a novel sensing platform for biomolecules, Chem. Commun. 49 (13) (2013) 1276-1278, https://doi.org/10.1039/c2cc36661d.

[102] K. Tabatabaeian, M. Simayee, A. Fallah-Shojaie, F. Mashayekhi, N-doped carbon nanodots@UiO-66- NH₂ as novel nanoparticles for releasing of the bioactive drug, rosmarinic acid and fluorescence imaging, Daru 27 (2019) 307-315, https://doi.org/10.1007/s40199-019-00276-1.

[103] J.M. Fang, F. Leng, X.J. Zhao, X.L. Hu, Y.F. Li, Metal-organic framework MIL-101 as a low background signal platform for label-free DNA detection, Analyst 139 (4) (2014) 801-806, https://doi.org/10.1039/c3an01975f.

[104] Y.L. Liu, W.L. Fu, C.M. Li, C.Z. Huang, Y.F. Li, Gold nanoparticles immobilized on metal-organic frameworks with enhanced catalytic performance for DNA detection, Anal. Chim. Acta 861 (2015) 55-61, https://doi.org/10.1016/j.aca.2014.12.032.

[105] H.-T. Zhang, J.-W. Zhang, G. Huang, Z.-Y. Du, H.-L. Jiang, An aminefunctionalized metal-organic framework as a sensing platform for DNA detection, Chem. Commun. 50 (81) (2014) 12069-12072, https://doi.org/10.1039/c4cc05571c.

[106] R.K. Alavijeh, S. Beheshti, K. Akhbari, A. Morsali, Investigation of reasons for metal-organic framework's antibacterial activities, Polyhedron 156 (2018) 257-278, https://doi.org/10.1016/j.poly.2018.09.028.

[107] N. Kaur, P. Tiwari, K.S. Kapoor, A.K. Saini, V. Sharma, S.M. Mobin, Metal-organic framework based antibiotic release and antimicrobial response: an overview, CrystEngComm 22 (44) (2020) 7513-7527, https://doi.org/10.1039/d0ce01215g.

[108] D.F. Sava Gallis, K.S. Butler, J.O. Agola, C.J. Pearce, A.A. McBride, Antibacterial countermeasures via metal-organic framework-supported sustained therapeutic release, ACS Appl. Mater. Interfaces 11 (8) (2019) 7782-7791, https://doi.org/10.1021/acsami.8b21698.

[109] Z. Yang, R. Qin, D. Ruan, C. Hu, W. Li, J. Zhou, F. Zhang, B. Guo, L. Huang, D. Jaque, Y. Shen, F. Wang, Ce6-DNAzyme-Loaded metal-organic framework theranostic agents for boosting miRNA imaging-guided photodynamic therapy in breast cancer, ACS Nano 19 (30) (2025) 27873-27889, https://doi.org/10.1021/acsnano.5c09287.

[110] Y. Pu, H. Yin, C. Dong, H. Xiang, W. Wu, B. Zhou, D. Du, Y. Chen, H. Xu, SonoControllable and ROS-Sensitive CRISPR-Cas 9 genome editing for Augmented/ Synergistic ultrasound tumor nanotherapy, Adv. Mater. (Deerfield Beach, Fla.) 33 (45) (2021) e2104641, https://doi.org/10.1002/adma.202104641.

[111] Y. Inokuma, S. Yoshioka, J. Ariyoshi, T. Arai, Y. Hitora, K. Takada, S. Matsunaga, K. Rissanen, M. Fujita, X-ray analysis on the nanogram to microgram scale using porous complexes, Nature 495 (7442) (2013) 461-466, https://doi.org/10.1038/nature11990.

[112] S. Lee, E.A. Kapustin, O.M. Yaghi, Coordinative alignment of molecules in chiral metal-organic frameworks, Science 353 (6301) (2016) 808-811, https://doi.org/10.1126/science.aaf9135.

[113] C. Ma, C. Lin, J. Li, MicroED as a powerful technique for the structure determination of complex porous materials, Chin. J. Struct. Chem. 43 (3) (2024) 100209, https://doi.org/10.1016/j.cjsc.2023.100209.

[114] E. Biehler, S. Pagola, D. Stam, J. Merkelbach, C. Jandl, T.M. Abdel-Fattah, A comparison of microcrystal electron diffraction and X-ray powder diffraction for the structural analysis of metal-organic frameworks, J. Appl. Crystallogr. 58 (2) (2025) 398-411, https://doi.org/10.1107/S1600576724012068.

[115] E. Danelius, K. Patel, B. Gonzalez, T. Gonen, MicroED in drug discovery, Curr. Opin. Struct. Biol. 79 (2023) 102549, https://doi.org/10.1016/j.sbi.2023.102549.

[116] C. Wang, T. Zhang, L.-X. Sun, Y.-H. Xing, F.-Y. Bai, Multi-stimulus responsive properties of a Cd-MOF based on tetraphenylethylene, Inorg. Chem. Front. 10 (24) (2023) 7351-7358, https://doi.org/10.1039/D3QI01954C.

[117] Y.D. Li, L.F. Ma, G.P. Yang, Y.Y. Wang, Photochromic metal-organic frameworks based on host-guest strategy and different viologen derivatives for organic amines sensing and information anticounterfeiting, Angew. Chem. Int. Ed. 137 (11) (2025) e202421744, https://doi.org/10.1002/anie.202421744.

[118] Z.Q. Yao, K. Wang, R. Liu, Y.J. Yuan, J.J. Pang, Q.W. Li, T.Y. Shao, Z.G. Li, R. Feng, B. Zou, Dynamic full-color tuning of organic chromophore in a Multi-Stimuli-responsive 2D flexible MOF, Angew. Chem. Int. Ed. 61 (17) (2022) e202202073, https://doi.org/10.1002/anie.202202073.

[119] X. Liu, X. Sun, Y. Peng, Y. Wang, D. Xu, W. Chen, W. Wang, X. Yan, X. Ma, Intrinsic properties enabled metal organic framework micromotors for highly efficient self-propulsion and enhanced antibacterial therapy, ACS Nano 16 (9) (2022) 14666-14678, https://doi.org/10.1021/acsnano.2c05295.

[120] J. Yu, Y. Li, A. Yan, Y. Gao, F. Xiao, Z. Xu, J. Xu, S. Yu, J. Liu, H. Sun, Selfpropelled enzymatic nanomotors from prodrug-skeletal zeolitic imidazolate frameworks for boosting multimodel cancer therapy efficiency, Adv. Sci. 10 (22) (2023) 2301919, https://doi.org/10.1002/advs.202301919.

[121] Z. Guo, C. Zhuang, Y. Song, J. Yong, Y. Li, Z. Guo, B. Kong, J.M. Whitelock, J. Wang, K. Liang, Biocatalytic buoyancy-driven nanobots for autonomous cell recognition and enrichment, Nano-Micro Lett. 15 (1) (2023) 236, https://doi.org/10.1007/s40820-023-01207-1.

[122] H. Huang, J. Li, M. Yuan, H. Yang, Y. Zhao, Y. Ying, S. Wang, Large-scale selfassembly of MOFs colloidosomes for bubble-propelled micromotors and stirringfree environmental remediation, Adv. Funct. Mater. 61 (46) (2022) e202211163, https://doi.org/10.1002/adfm.202204946.

[123] Q. Sun, H. Bi, Z. Wang, C. Li, X. Wang, J. Xu, H. Zhu, R. Zhao, F. He, S. Gai, Hyaluronic acid-targeted and pH -responsive drug delivery system based on metalorganic frameworks for efficient antitumor therapy, Biomaterials 223 (2019) 119473, https://doi.org/10.1016/j.biomaterials.2019.119473.

[124] Z. Rahmati, J. Abdi, M. Vossoughi, I. Alemzadeh, Ag-doped magnetic metal organic framework as a novel nanostructured material for highly efficient antibacterial activity, Environ. Res. 188 (2020) 109555, https://doi.org/10.1016/j.envres.2020.109555.

[125] X. Wei, X. Kong, S. Wang, H. Xiang, J. Wang, J. Chen, Removal of heavy metals from electroplating wastewater by thin-film composite nanofiltration hollow-fiber membranes, Ind. Eng. Chem. Res. 52 (49) (2013) 17583-17590, https://doi.org/10.1021/ie402387u.

[126] X. Ge, Y. Liu, X. Zhao, A. Nafady, G. Bhattacharya, J. Mai, A.M. Al-Enizi, R. I. Pettigrew, S. Ma, Advances in metal-organic frameworks for cardiovascular therapy: from structural design to preclinical applications, Adv. Sci. 544 (2025) 216971, https://doi.org/10.1002/advs.202416302.

[127] W. Ni, L. Zhang, H. Zhang, C. Zhang, K. Jiang, X. Cao, Hierarchical MOF-on-MOF architecture for pH/GSH-Controlled drug delivery and Fe-Based chemodynamic therapy, Inorg. Chem. 61 (7) (2022) 3281-3287, https://doi.org/10.1021/acs.inorgchem.1c03855.

[128] F. Melle, D. Menon, J. Conniot, J. Ostolaza-Paraiso, S. Mercado, J. Oliveira, X. Chen, B.B. Mendes, J. Conde, D. Fairen-Jimenez, Rational design of metal-organic frameworks for pancreatic cancer therapy: from machine learning screening to in vivo efficacy, Adv. Mater. (2025), https://doi.org/10.1002/adma.202412757.

[129] K. Xing, R. Fan, F. Wang, H. Nie, X. Du, S. Gai, P. Wang, Y. Yang, Dual-stimulustriggered programmable drug release and luminescent ratiometric pH sensing from chemically stable biocompatible zinc metal-organic framework, ACS Appl. Mater. Interfaces 10 (26) (2018) 22746-22756, https://doi.org/10.1021/acsami.8b06270.

[130] F. Reichmayr, D. Wolf, G. Zhang, M. Wang, M. Herzog, R. Dong, X. Feng, A. Lubk, I. Weidinger, Raman marker bands for In-situ quality control during synthesis of two-dimensional conjugated metal-organic frameworks, ChemRxiv (2024), https://doi.org/10.26434/chemrxiv-2024-tqcg9.

[131] X. Chen, Y. Zhuang, N. Rampal, R. Hewitt, G. Divitini, C.A. O'Keefe, X. Liu, D. J. Whitaker, J.W. Wills, R. Jugdaohsingh, Formulation of metal-organic framework-based drug carriers by controlled coordination of methoxy PEG phosphate: boosting colloidal stability and redispersibility, J. Am. Chem. Soc. 143 (34) (2021) 13557-13572, https://doi.org/10.1021/jacs.1c03943.

[132] Z. Xu, Y. Liu, D. Wang, S. Yan, Y. Xu, X. Wang, Q. Li, Defective MOFs as nano carrier for drug loading with controlled release, Colloids Surf. A Physicochem. Eng. Asp. 697 (2024) 134427, https://doi.org/10.1016/j.colsurfa.2024.134427.

[133] L. Yang, H. Chen, A.E. Kaziem, X. Miao, S. Huang, D. Cheng, H. Xu, Z. Zhang, Effects of exposure to different types of metal-organic framework nanoparticles on the gut microbiota and liver metabolism of adult zebrafish, ACS Nano 18 (37) (2024) 25425-25445, https://doi.org/10.1021/acsnano.4c03451.

[134] C.-H. Liu, H.-C. Chiu, H.-L. Sung, J.-Y. Yeh, K.C.-W. Wu, S.-H. Liu, Acute oral toxicity and repeated dose 28-day oral toxicity studies of MIL-101 nanoparticles, Regul. Toxicol. Pharmacol. 107 (2019) 104426, https://doi.org/10.1016/j.yrtph.2019.104426.

[135] T. Baati, L. Njim, F. Neffati, A. Kerkeni, M. Bouttemi, R. Gref, M.F. Najjar, A. Zakhama, P. Couvreur, C. Serre, In depth analysis of the in vivo toxicity of nanoparticles of porous iron (III) metal-organic frameworks, Royal Soc. Chem. 4 (4) (2013) 1597-1607, https://doi.org/10.1039/c3sc22116d,2013.

[136] H. Wang, D. Yu, J. Fang, C. Cao, Z. Liu, J. Ren, X. Qu, Renal-clearable porphyrinic metal-organic framework nanodots for enhanced photodynamic therapy, ACS Nano 13 (8) (2019) 9206-9217, https://doi.org/10.1021/acsnano.9b03531.

[137] J. Shan, L. Du, X. Wang, S. Zhang, Y. Li, S. Xue, Q. Tang, P. Liu, Ultrasound trigger ce-based MOF nanoenzyme for efficient thrombolytic therapy, Adv. Sci. 11 (20) (2024) 2304441, https://doi.org/10.1002/advs.202304441.

[138] M. Koshy, M. Spiotto, L.E. Feldman, J.J. Luke, G.F. Fleming, D. Olson, J. W. Moroney, R. Nanda, A. Rosenberg, A.T. Pearson, A phase 1 dose-escalation study of RiMO-301 with palliative radiation in advanced tumors, J. Clin. Oncol. 41 (2023) 2527, https://doi.org/10.1200/JCO.2023.41.16_suppl.2527.