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Metal–organic frameworks for biological applications

Nature Reviews Methods Primers volume 4, Article number: 42 (2024) Cite this article

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Abstract

Metal–organic frameworks (MOFs) have emerged as exciting potential new candidates for application across nanomedicine, with the first example now in a phase II human clinical trial. MOFs have a range of desirable properties that make them suitable for various applications, including drug delivery, imaging and new treatment modalities, often in concert. In this Primer, we present an overview of the application of MOFs in biomedicine, focusing on drug delivery and imaging, but highlighting the chemical and structural versatility that is enabling their implementation in emerging treatment modalities and new biological applications. We discuss best practices in synthesis, characterization and application, including ongoing issues with reproducibility and limitations of applications, ending with an outlook of the field.

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Fig. 1: Schematic overview of the biomedical applications of metal–organic frameworks based on their composition.
Fig. 2: An overview of practical and synthetic considerations when selecting a metal–organic framework for a particular biological application.
Fig. 3: The loading and release of cargo from nanoparticulate metal–organic frameworks.
Fig. 4: Recommended workflow for physicochemical characterization of nanoparticulate metal–organic frameworks for biological applications.
Fig. 5: Overview of analytical methodologies that can be used to assess the biological behaviour of nanoparticulate metal–organic frameworks in a research laboratory context, with example data.
Fig. 6: Exemplar studies of nanoparticulate metal–organic frameworks in biomedical applications.
Fig. 7: Emerging frontier biomedical applications of metal–organic frameworks.

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References

  1. Vargason, A. M., Anselmo, A. C. & Mitragotri, S. The evolution of commercial drug delivery technologies. Nat. Biomed. Eng. 5, 951–967 (2021).

    Article  Google Scholar 

  2. Mitchell, M. J. et al. Engineering precision nanoparticles for drug delivery. Nat. Rev. Drug Discov. 20, 101–124 (2021).

    Article  Google Scholar 

  3. Sercombe, L. et al. Advances and challenges of liposome assisted drug delivery. Front. Pharmacol. 6, 286 (2015).

    Article  Google Scholar 

  4. Naseri, N., Valizadeh, H. & Zakeri-Milani, P. Solid lipid nanoparticles and nanostructured lipid carriers: structure, preparation and application. Adv. Pharm. Bull. 5, 305–313 (2015).

    Article  Google Scholar 

  5. Demir Duman, F. et al. in Biomedical Applications of Inorganic Materials Ch. 2, 14–126 (The Royal Society of Chemistry, 2021).

  6. Unnikrishnan, G., Joy, A., Megha, M., Kolanthai, E. & Senthilkumar, M. Exploration of inorganic nanoparticles for revolutionary drug delivery applications: a critical review. Discov. Nano 18, 157 (2023).

    Article  Google Scholar 

  7. Moore, T. L. et al. Nanoparticle colloidal stability in cell culture media and impact on cellular interactions. Chem. Soc. Rev. 44, 6287–6305 (2015).

    Article  Google Scholar 

  8. Furukawa, H., Cordova, K. E., O’Keeffe, M. & Yaghi, O. M. The chemistry and applications of metal–organic frameworks. Science 341, 1230444 (2013).

    Article  Google Scholar 

  9. Lawson, H. D., Walton, S. P. & Chan, C. Metal–organic frameworks for drug delivery: a design perspective. ACS Appl. Mater. Interfaces 13, 7004–7020 (2021).

    Article  Google Scholar 

  10. Rojas, S., Devic, T. & Horcajada, P. Metal–organic frameworks based on bioactive components. J. Mater. Chem. B 5, 2560–2573 (2017).

    Article  Google Scholar 

  11. Cai, H., Huang, Y.-L. & Li, D. Biological metal–organic frameworks: structures, host–guest chemistry and bio-applications. Coord. Chem. Rev. 378, 207–221 (2019).

    Article  Google Scholar 

  12. Bunzen, H. Chemical stability of metal–organic frameworks for applications in drug delivery. ChemNanoMat 7, 998–1007 (2021).

    Article  Google Scholar 

  13. Ettlinger, R. et al. Toxicity of metal–organic framework nanoparticles: from essential analyses to potential applications. Chem. Soc. Rev. 51, 464–484 (2022). A comprehensive overview of the varying factors dictating metal–organic framework toxicity and how to assess it in vitro and in vivo.

    Article  Google Scholar 

  14. Osterrieth, J. W. M. & Fairen-Jimenez, D. Metal–organic framework composites for theragnostics and drug delivery applications. Biotechnol. J. 16, 2000005 (2021).

    Article  Google Scholar 

  15. Wang, A. et al. Biomedical metal–organic framework materials: perspectives and challenges. Adv. Funct. Mater. https://doi.org/10.1002/adfm.202308589 (2023).

  16. Horcajada, P. et al. Metal–organic frameworks as efficient materials for drug delivery. Angew. Chem. Int. Ed. 45, 5974–5978 (2006).

    Article  Google Scholar 

  17. Horcajada, P. et al. Flexible porous metal–organic frameworks for a controlled drug delivery. J. Am. Chem. Soc. 130, 6774–6780 (2008).

    Article  Google Scholar 

  18. Xiao, B. et al. High-capacity hydrogen and nitric oxide adsorption and storage in a metal−organic framework. J. Am. Chem. Soc. 129, 1203–1209 (2007).

    Article  Google Scholar 

  19. McKinlay, A. C. et al. Exceptional behavior over the whole adsorption−storage−delivery cycle for NO in porous metal organic frameworks. J. Am. Chem. Soc. 130, 10440–10444 (2008).

    Article  Google Scholar 

  20. Taylor, K. M. L., Rieter, W. J. & Lin, W. Manganese-based nanoscale metal−organic frameworks for magnetic resonance imaging. J. Am. Chem. Soc. 130, 14358–14359 (2008).

    Article  Google Scholar 

  21. Rowe, M. D., Thamm, D. H., Kraft, S. L. & Boyes, S. G. Polymer-modified gadolinium metal–organic framework nanoparticles used as multifunctional nanomedicines for the targeted imaging and treatment of cancer. Biomacromolecules 10, 983–993 (2009).

    Article  Google Scholar 

  22. Rieter, W. J., Taylor, K. M. L., An, H., Lin, W. & Lin, W. Nanoscale metal−organic frameworks as potential multimodal contrast enhancing agents. J. Am. Chem. Soc. 128, 9024–9025 (2006).

    Article  Google Scholar 

  23. McKinlay, A. C. et al. BioMOFs: metal–organic frameworks for biological and medical applications. Angew. Chem. Int. Ed. 49, 6260–6266 (2010).

    Article  Google Scholar 

  24. Horcajada, P. et al. Porous metal–organic-framework nanoscale carriers as a potential platform for drug delivery and imaging. Nat. Mater. 9, 172–178 (2010). A major breakthrough study demonstrating drug delivery and MRI using Fe metal–organic frameworks in vitro and in vivo.

    Article  ADS  Google Scholar 

  25. Horcajada, P. et al. Metal–organic frameworks in biomedicine. Chem. Rev. 112, 1232–1268 (2012).

    Article  Google Scholar 

  26. Liu, X. et al. Iron-based metal–organic frameworks in drug delivery and biomedicine. ACS Appl. Mater. Interfaces 13, 9643–9655 (2021).

    Article  Google Scholar 

  27. Abánades Lázaro, I. & Forgan, R. S. Application of zirconium MOFs in drug delivery and biomedicine. Coord. Chem. Rev. 380, 230–259 (2019).

    Article  Google Scholar 

  28. Wang, J. et al. Advances of hafnium based nanomaterials for cancer theranostics. Front. Chem. 11, 1283924 (2023).

    Article  ADS  Google Scholar 

  29. Wang, Q., Sun, Y., Li, S., Zhang, P. & Yao, Q. Synthesis and modification of ZIF-8 and its application in drug delivery and tumor therapy. RSC Adv. 10, 37600–37620 (2020).

    Article  ADS  Google Scholar 

  30. Maleki, A., Shahbazi, M.-A., Alinezhad, V. & Santos, H. A. The progress and prospect of zeolitic imidazolate frameworks in cancer therapy, antibacterial activity, and biomineralization. Adv. Healthc. Mater. 9, 2000248 (2020).

    Article  Google Scholar 

  31. Demir Duman, F. & Forgan, R. S. Applications of nanoscale metal–organic frameworks as imaging agents in biology and medicine. J. Mater. Chem. B 9, 3423–3449 (2021).

    Article  Google Scholar 

  32. Lu, K., Aung, T., Guo, N., Weichselbaum, R. & Lin, W. Nanoscale metal–organic frameworks for therapeutic, imaging, and sensing applications. Adv. Mater. 30, 1707634 (2018).

    Article  Google Scholar 

  33. Zhu, W., Zhao, J., Chen, Q. & Liu, Z. Nanoscale metal–organic frameworks and coordination polymers as theranostic platforms for cancer treatment. Coord. Chem. Rev. 398, 113009 (2019).

    Article  Google Scholar 

  34. Ni, K., Lan, G. & Lin, W. Nanoscale metal–organic frameworks generate reactive oxygen species for cancer therapy. ACS Cent. Sci. 6, 861–868 (2020).

    Article  Google Scholar 

  35. Yin, X., Ai, F. & Han, L. Recent development of MOF-based photothermal agent for tumor ablation. Front. Chem. 10, 841316 (2022).

    Article  Google Scholar 

  36. Zhong, Y. et al. Recent advances in MOF-based nanoplatforms generating reactive species for chemodynamic therapy. Dalton Trans. 49, 11045–11058 (2020).

    Article  Google Scholar 

  37. Koshy, M. et al. A phase 1 dose–escalation study of RiMO-301 with palliative radiation in advanced tumors. J. Clin. Oncol. 41, 2527–2527 (2023). A report covering the first human clinical trial involving a metal–organic framework.

    Article  Google Scholar 

  38. Tyagi, N., Wijesundara, Y. H., Gassensmith, J. J. & Popat, A. Clinical translation of metal–organic frameworks. Nat. Rev. Mater. 8, 701–703 (2023).

    Article  ADS  Google Scholar 

  39. Allendorf, M. D., Stavila, V., Witman, M., Brozek, C. K. & Hendon, C. H. What lies beneath a metal–organic framework crystal structure? New design principles from unexpected behaviors. J. Am. Chem. Soc. 143, 6705–6723 (2021).

    Article  Google Scholar 

  40. Pearson, R. G. Hard and soft acids and bases. J. Am. Chem. Soc. 85, 3533–3539 (1963).

    Article  Google Scholar 

  41. He, T., Kong, X.-J. & Li, J.-R. Chemically stable metal–organic frameworks: rational construction and application expansion. Acc. Chem. Res. 54, 3083–3094 (2021).

    Article  Google Scholar 

  42. Bůžek, D., Adamec, S., Lang, K. & Demel, J. Metal–organic frameworks vs. buffers: case study of UiO-66 stability. Inorg. Chem. Front. 8, 720–734 (2021).

    Article  Google Scholar 

  43. Luzuriaga, M. A. et al. ZIF-8 degrades in cell media, serum, and some — but not all — common laboratory buffers. Supramol. Chem. 31, 485–490 (2019).

    Article  Google Scholar 

  44. McGuire, C. V. & Forgan, R. S. The surface chemistry of metal–organic frameworks. Chem. Commun. 51, 5199–5217 (2015).

    Article  Google Scholar 

  45. Figueroa-Quintero, L. et al. Post-synthetic surface modification of metal–organic frameworks and their potential applications. Small Methods 7, 2201413 (2023).

    Article  Google Scholar 

  46. Chen, X. et al. 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, 13557–13572 (2021).

    Article  Google Scholar 

  47. Abánades Lázaro, I. et al. Selective surface PEGylation of UiO-66 nanoparticles for enhanced stability, cell uptake, and pH-responsive drug delivery. Chem 2, 561–578 (2017).

    Article  Google Scholar 

  48. Howarth, A. J. et al. Best practices for the synthesis, activation, and characterization of metal–organic frameworks. Chem. Mater. 29, 26–39 (2017).

    Article  ADS  Google Scholar 

  49. Wang, S., McGuirk, C. M., d’Aquino, A., Mason, J. A. & Mirkin, C. A. Metal–organic framework nanoparticles. Adv. Mater. 30, 1800202 (2018).

    Article  Google Scholar 

  50. Marshall, C. R., Staudhammer, S. A. & Brozek, C. K. Size control over metal–organic framework porous nanocrystals. Chem. Sci. 10, 9396–9408 (2019). A comprehensive perspective on methods to control particle size of nanoparticulate metal–organic frameworks.

    Article  Google Scholar 

  51. Forgan, R. S. Modulated self-assembly of metal–organic frameworks. Chem. Sci. 11, 4546–4562 (2020). A detailed review of the use of modulation to control particle size and surface chemistry of nanoparticulate metal–organic frameworks.

    Article  Google Scholar 

  52. Wang, Z. et al. Surfactant-guided spatial assembly of nano-architectures for molecular profiling of extracellular vesicles. Nat. Commun. 12, 4039 (2021).

    Article  ADS  Google Scholar 

  53. Kumari, S. et al. In vivo biocompatibility of ZIF-8 for slow release via intranasal administration. Chem. Sci. 14, 5774–5782 (2023).

    Article  Google Scholar 

  54. Markopoulou, P. & Forgan, R. S. in Metal–Organic Frameworks for Biomedical Applications (ed. Mozafari, M.) Ch. 12, 245–276 (Woodhead Publishing, 2020).

  55. Giménez-Marqués, M. et al. GraftFast surface engineering to improve MOF nanoparticles furtiveness. Small 14, 1801900 (2018).

    Article  Google Scholar 

  56. Bellido, E. et al. Heparin-engineered mesoporous iron metal–organic framework nanoparticles: toward stealth drug nanocarriers. Adv. Healthc. Mater. 4, 1246–1257 (2015).

    Article  Google Scholar 

  57. Röder, R. et al. Multifunctional nanoparticles by coordinative self-assembly of his-tagged units with metal–organic frameworks. J. Am. Chem. Soc. 139, 2359–2368 (2017).

    Article  Google Scholar 

  58. Jung, S. et al. Bio-functionalization of metal–organic frameworks by covalent protein conjugation. Chem. Commun. 47, 2904–2906 (2011).

    Article  Google Scholar 

  59. Hidalgo, T. et al. Chitosan-coated mesoporous MIL-100(Fe) nanoparticles as improved bio-compatible oral nanocarriers. Sci. Rep. 7, 43099 (2017).

    Article  ADS  Google Scholar 

  60. Demir Duman, F., Monaco, A., Foulkes, R., Becer, C. R. & Forgan, R. S. Glycopolymer-functionalized MOF-808 nanoparticles as a cancer-targeted dual drug delivery system for carboplatin and floxuridine. ACS Appl. Nano Mater. 5, 13862–13873 (2022).

    Article  Google Scholar 

  61. Qiu, J. et al. Porous nanoparticles with engineered shells release their drug cargo in cancer cells. Int. J. Pharm. 610, 121230 (2021).

    Article  Google Scholar 

  62. Agostoni, V. et al. A ‘green’ strategy to construct non-covalent, stable and bioactive coatings on porous MOF nanoparticles. Sci. Rep. 5, 7925 (2015).

    Article  Google Scholar 

  63. Cutrone, G. et al. Comb-like dextran copolymers: a versatile strategy to coat highly porous MOF nanoparticles with a PEG shell. Carbohydr. Polym. 223, 115085 (2019).

    Article  Google Scholar 

  64. Morris, W., Briley, W. E., Auyeung, E., Cabezas, M. D. & Mirkin, C. A. Nucleic acid–metal organic framework (MOF) nanoparticle conjugates. J. Am. Chem. Soc. 136, 7261–7264 (2014).

    Article  Google Scholar 

  65. Kahn, J. S., Freage, L., Enkin, N., Garcia, M. A. A. & Willner, I. Stimuli-responsive DNA-functionalized metal–organic frameworks (MOFs). Adv. Mater. 29, 1602782 (2017).

    Article  Google Scholar 

  66. Wang, S. et al. General and direct method for preparing oligonucleotide-functionalized metal–organic framework nanoparticles. J. Am. Chem. Soc. 139, 9827–9830 (2017). Development of a simple, facile method for coating metal–organic framework nanoparticles with oligonucleotides through phosphate coordination.

    Article  Google Scholar 

  67. Wuttke, S. et al. MOF nanoparticles coated by lipid bilayers and their uptake by cancer cells. Chem. Commun. 51, 15752–15755 (2015).

    Article  Google Scholar 

  68. Li, X. et al. Drug-loaded lipid-coated hybrid organic–inorganic ‘stealth’ nanoparticles for cancer therapy. Front. Bioeng. Biotechnol. 8, 1027 (2020).

    Article  Google Scholar 

  69. Ding, M., Liu, W. & Gref, R. Nanoscale MOFs: from synthesis to drug delivery and theranostics applications. Adv. Drug Deliv. Rev. 190, 114496 (2022).

    Article  Google Scholar 

  70. He, S. et al. Metal–organic frameworks for advanced drug delivery. Acta Pharm. Sin. B 11, 2362–2395 (2021).

    Article  Google Scholar 

  71. Miller, S. R. et al. Biodegradable therapeutic MOFs for the delivery of bioactive molecules. Chem. Commun. 46, 4526–4528 (2010).

    Article  Google Scholar 

  72. Tamames-Tabar, C. et al. A Zn azelate MOF: combining antibacterial effect. CrystEngComm 17, 456–462 (2015).

    Article  Google Scholar 

  73. Su, H. et al. A highly porous medical metal–organic framework constructed from bioactive curcumin. Chem. Commun. 51, 5774–5777 (2015).

    Article  Google Scholar 

  74. Abánades Lázaro, I., Abánades Lázaro, S. & Forgan, R. S. Enhancing anticancer cytotoxicity through bimodal drug delivery from ultrasmall Zr MOF nanoparticles. Chem. Commun. 54, 2792–2795 (2018).

    Article  Google Scholar 

  75. Abánades Lázaro, I., Wells, C. J. R. & Forgan, R. S. Multivariate modulation of the Zr MOF UiO-66 for defect-controlled combination anticancer drug delivery. Angew. Chem. Int. Ed. 59, 5211–5217 (2020). Development of the defect-loading concept to maximize drug loading in metal–organic frameworks, including generating metal–organic framework nanoparticles loaded with four separate drugs.

    Article  Google Scholar 

  76. Zheng, H. et al. One-pot synthesis of metal–organic frameworks with encapsulated target molecules and their applications for controlled drug delivery. J. Am. Chem. Soc. 138, 962–968 (2016).

    Article  Google Scholar 

  77. Yan, J. et al. Mineralization of pH-sensitive doxorubicin prodrug in ZIF-8 to enable targeted delivery to solid tumors. Anal. Chem. 92, 11453–11461 (2020).

    Article  Google Scholar 

  78. Lyu, F., Zhang, Y., Zare, R. N., Ge, J. & Liu, Z. One-pot synthesis of protein-embedded metal–organic frameworks with enhanced biological activities. Nano Lett. 14, 5761–5765 (2014). Development of the one-pot encapsulation of proteins by zeolitic imidazolate frameworks.

    Article  ADS  Google Scholar 

  79. Dutta, S. et al. Nanoarchitectonics of biofunctionalized metal–organic frameworks with biological macromolecules and living cells. Small Methods 3, 1900213 (2019).

    Article  Google Scholar 

  80. Riccò, R. et al. Metal–organic frameworks for cell and virus biology: a perspective. ACS Nano 12, 13–23 (2018).

    Article  Google Scholar 

  81. Velásquez-Hernández, Md. J. et al. Towards applications of bioentities@MOFs in biomedicine. Coord. Chem. Rev. 429, 213651 (2021).

    Article  Google Scholar 

  82. Cases Díaz, J., Lozano-Torres, B. & Giménez-Marqués, M. Boosting protein encapsulation through Lewis-acid-mediated metal–organic framework mineralization: toward effective intracellular delivery. Chem. Mater. 34, 7817–7827 (2022).

    Article  Google Scholar 

  83. Agostoni, V. et al. Towards an improved anti-HIV activity of NRTI via metal–organic frameworks nanoparticles. Adv. Healthc. Mater. 2, 1630–1637 (2013).

    Article  Google Scholar 

  84. Souza, B. E. & Tan, J.-C. Mechanochemical approaches towards the in situ confinement of 5-FU anti-cancer drug within MIL-100 (Fe) metal–organic framework. CrystEngComm 22, 4526–4530 (2020).

    Article  Google Scholar 

  85. Orellana-Tavra, C. et al. Amorphous metal–organic frameworks for drug delivery. Chem. Commun. 51, 13878–13881 (2015).

    Article  Google Scholar 

  86. Chakraborty, D., Yurdusen, A., Mouchaham, G., Nouar, F. & Serre, C. Large-scale production of metal–organic frameworks. Adv. Funct. Mater. https://doi.org/10.1002/adfm.202309089 (2023).

    Article  Google Scholar 

  87. Giménez-Marqués, M., Hidalgo, T., Serre, C. & Horcajada, P. Nanostructured metal–organic frameworks and their bio-related applications. Coord. Chem. Rev. 307, 342–360 (2016).

    Article  Google Scholar 

  88. Khan, N. A. & Jhung, S. H. Synthesis of metal-organic frameworks (MOFs) with microwave or ultrasound: rapid reaction, phase-selectivity, and size reduction. Coord. Chem. Rev. 285, 11–23 (2015).

    Article  Google Scholar 

  89. Tanaka, S. in Metal–Organic Frameworks for Biomedical Applications (ed. Mozafari, M.) Ch. 10, 197–222 (Woodhead Publishing, 2020).

  90. Rubio-Martinez, M. et al. New synthetic routes towards MOF production at scale. Chem. Soc. Rev. 46, 3453–3480 (2017).

    Article  Google Scholar 

  91. Osterrieth, J. W. M. et al. How reproducible are surface areas calculated from the BET equation. Adv. Mater. 34, 2201502 (2022). An interlaboratory study of porosity analysis procedures that led to the development of novel, open-source analytical software.

    Article  Google Scholar 

  92. Lázaro, I. A. A comprehensive thermogravimetric analysis multifaceted method for the exact determination of the composition of multifunctional metal–organic framework materials. Eur. J. Inorg. Chem. 2020, 4284–4294 (2020).

    Article  Google Scholar 

  93. Christodoulou, I. et al. Nanoscale iron-based metal–organic frameworks: incorporation of functionalized drugs and degradation in biological media. Int. J. Mol. Sci. 24, 3662 (2023).

    Article  Google Scholar 

  94. Hirschle, P. et al. Exploration of MOF nanoparticle sizes using various physical characterization methods — is what you measure what you get. CrystEngComm 18, 4359–4368 (2016).

    Article  Google Scholar 

  95. Wheeler, K. E. et al. Environmental dimensions of the protein corona. Nat. Nanotechnol. 16, 617–629 (2021).

    Article  ADS  Google Scholar 

  96. Li, X. et al. Doxorubicin-loaded metal–organic frameworks nanoparticles with engineered cyclodextrin coatings: insights on drug location by solid state NMR spectroscopy. Nanomaterials 11, 945 (2021).

    Article  ADS  Google Scholar 

  97. Cunha, D. et al. Rationale of drug encapsulation and release from biocompatible porous metal–organic frameworks. Chem. Mater. 25, 2767–2776 (2013).

    Article  Google Scholar 

  98. Motakef-Kazemi, N., Shojaosadati, S. A. & Morsali, A. Metal organic framework [Zn2(1,4-bdc)2(dabco)]n as drug delivery system. Adv. Mater. Res. 829, 247–250 (2014).

    Article  Google Scholar 

  99. Markopoulou, P. et al. Identifying differing intracellular cargo release mechanisms by monitoring in vitro drug delivery from MOFs in real time. Cell Rep. Phys. Sci. 1, 100254 (2020).

    Article  Google Scholar 

  100. Hu, Z. et al. A luminescent Mg-metal–organic framework for sustained release of 5-fluorouracil: appropriate host–guest interaction and satisfied acid–base resistance. ACS Appl. Mater. Interfaces 12, 14914–14923 (2020).

    Article  Google Scholar 

  101. Modi, S. & Anderson, B. D. Determination of drug release kinetics from nanoparticles: overcoming pitfalls of the dynamic dialysis method. Mol. Pharm. 10, 3076–3089 (2013).

    Article  Google Scholar 

  102. Porcino, M., Li, X., Gref, R. & Martineau-Corcos, C. Solid-state NMR spectroscopy: a key tool to unravel the supramolecular structure of drug delivery systems. Molecules 26, 4142 (2021).

    Article  Google Scholar 

  103. Chaupard, M., de Frutos, M. & Gref, R. Deciphering the structure and chemical composition of drug nanocarriers: from bulk approaches to individual nanoparticle characterization. Part. Part. Syst. Charact. 38, 2100022 (2021).

    Article  Google Scholar 

  104. Bhattacharjee, A., Gumma, S. & Purkait, M. K. Fe3O4 promoted metal–organic framework MIL-100(Fe) for the controlled release of doxorubicin hydrochloride. Microporous Mesoporous Mater. 259, 203–210 (2018).

    Article  Google Scholar 

  105. Ke, X., Song, X., Qin, N., Cai, Y. & Ke, F. Rational synthesis of magnetic Fe3O4@MOF nanoparticles for sustained drug delivery. J. Porous Mater. 26, 813–818 (2019).

    Article  Google Scholar 

  106. Fytory, M. et al. Dual-ligated metal–organic framework as novel multifunctional nanovehicle for targeted drug delivery for hepatic cancer treatment. Sci. Rep. 11, 19808 (2021).

    Article  ADS  Google Scholar 

  107. di Nunzio, M. R., Agostoni, V., Cohen, B., Gref, R. & Douhal, A. A ‘ship in a bottle’ strategy to load a hydrophilic anticancer drug in porous metal–organic framework nanoparticles: efficient encapsulation, matrix stabilization, and photodelivery. J. Med. Chem. 57, 411–420 (2014).

    Article  Google Scholar 

  108. Jiang, K. et al. Thermal stimuli-triggered drug release from a biocompatible porous metal–organic framework. Chem. Eur. J. 23, 10215–10221 (2017).

    Article  Google Scholar 

  109. Kaur, N. et al. Metal–organic framework based antibiotic release and antimicrobial response: an overview. CrystEngComm 22, 7513–7527 (2020).

    Article  Google Scholar 

  110. Wang, Y. et al. Metal–organic frameworks for stimuli-responsive drug delivery. Biomaterials 230, 119619 (2020).

    Article  Google Scholar 

  111. Rodriguez-Ruiz, V. et al. Efficient ‘green’ encapsulation of a highly hydrophilic anticancer drug in metal–organic framework nanoparticles. J. Drug Target. 23, 759–767 (2015).

    Article  Google Scholar 

  112. Segeritz, C.-P. & Vallier, L. in Basic Science Methods for Clinical Researchers (eds Jalali, M., Saldanha, F. Y. L. & Jalali, M.) Ch. 9, 151–172 (Academic Press, 2017).

  113. Jennings, P. ‘The future of in vitro toxicology’. Toxicol. In Vitro 29, 1217–1221 (2015).

    Article  Google Scholar 

  114. Nikolic, M., Sustersic, T. & Filipovic, N. In vitro models and on-chip systems: biomaterial interaction studies with tissues generated using lung epithelial and liver metabolic cell lines. Front. Bioeng. Biotechnol. 6, 120 (2018).

    Article  Google Scholar 

  115. Zhu, D., Long, Q., Xu, Y. & Xing, J. Evaluating nanoparticles in preclinical research using microfluidic systems. Micromachines 10, 414 (2019).

    Article  Google Scholar 

  116. Langhans, S. A. Three-dimensional in vitro cell culture models in drug discovery and drug repositioning. Front. Pharmacol. 9, 6 (2018).

    Article  Google Scholar 

  117. Linnane, E., Haddad, S., Melle, F., Mei, Z. & Fairen-Jimenez, D. The uptake of metal–organic frameworks: a journey into the cell. Chem. Soc. Rev. 51, 6065–6086 (2022).

    Article  Google Scholar 

  118. Ernsting, M. J., Murakami, M., Roy, A. & Li, S.-D. Factors controlling the pharmacokinetics, biodistribution and intratumoral penetration of nanoparticles. J. Control. Rel. 172, 782–794 (2013).

    Article  Google Scholar 

  119. Park, J., Jiang, Q., Feng, D., Mao, L. & Zhou, H.-C. Size-controlled synthesis of porphyrinic metal–organic framework and functionalization for targeted photodynamic therapy. J. Am. Chem. Soc. 138, 3518–3525 (2016).

    Article  Google Scholar 

  120. Elliott, A. D. Confocal microscopy: principles and modern practices. Curr. Protoc. Cytom. 92, e68 (2020).

    Article  Google Scholar 

  121. Paddock, S. W. & Eliceiri, K. W. in Confocal Microscopy: Methods and Protocols (ed. Paddock, S. W.) Ch. 2, 9–47 (Springer New York, 2014).

  122. Sava Gallis, D. F., Butler, K. S., Agola, J. O., Pearce, C. J. & McBride, A. A. Antibacterial countermeasures via metal–organic framework-supported sustained therapeutic release. ACS Appl. Mater. Interfaces 11, 7782–7791 (2019).

    Article  Google Scholar 

  123. McKinnon, K. M. Flow cytometry: an overview. Curr. Protoc. Immunol. 120, 5.1.1–5.1.11 (2018).

    Article  Google Scholar 

  124. Suzuki, H., Toyooka, T. & Ibuki, Y. Simple and easy method to evaluate uptake potential of nanoparticles in mammalian cells using a flow cytometric light scatter analysis. Environ. Sci. Technol. 41, 3018–3024 (2007).

    Article  ADS  Google Scholar 

  125. Orellana-Tavra, C. et al. Tuning the endocytosis mechanism of Zr-based metal–organic frameworks through linker functionalization. ACS Appl. Mater. Interfaces 9, 35516–35525 (2017). A discussion of the effect of metal–organic framework surface chemistry on different endocytosis pathways to optimize in vitro drug delivery efficacy.

    Article  Google Scholar 

  126. Cornelissen, M., Philippé, J., De Sitter, S. & De Ridder, L. Annexin V expression in apoptotic peripheral blood lymphocytes: an electron microscopic evaluation. Apoptosis 7, 41–47 (2002).

    Article  Google Scholar 

  127. Luo, T. et al. Dimensional reduction enhances photodynamic therapy of metal–organic nanophotosensitizers. J. Am. Chem. Soc. 144, 5241–5246 (2022).

    Article  Google Scholar 

  128. Singh, N., Qutub, S. & Khashab, N. M. Biocompatibility and biodegradability of metal–organic frameworks for biomedical applications. J. Mater. Chem. B 9, 5925–5934 (2021).

    Article  Google Scholar 

  129. Carrillo-Carrión, C. et al. Plasmonic-assisted thermocyclizations in living cells using metal–organic framework based nanoreactors. ACS Nano 15, 16924–16933 (2021).

    Article  Google Scholar 

  130. Jafari, S. et al. Human plasma protein corona decreases the toxicity of pillar-layer metal organic framework. Sci. Rep. 10, 14569 (2020).

    Article  ADS  Google Scholar 

  131. Li, R. et al. Solvent-free cyanosilylation of aldehydes and anti-cervical cancer activity of a highly porous zinc-MOF. J. Clust. Sci. 30, 1683–1691 (2019).

    Article  ADS  Google Scholar 

  132. Jiao, G. et al. Limitations of MTT and CCK-8 assay for evaluation of graphene cytotoxicity. RSC Adv. 5, 53240–53244 (2015).

    Article  ADS  Google Scholar 

  133. Mukherjee, P., Roy, S., Ghosh, D. & Nandi, S. K. Role of animal models in biomedical research: a review. Lab. Anim. Res. 38, 18 (2022).

    Article  Google Scholar 

  134. Valcourt, D. M., Kapadia, C. H., Scully, M. A., Dang, M. N. & Day, E. S. Best practices for preclinical in vivo testing of cancer nanomedicines. Adv. Healthc. Mater. 9, 2000110 (2020).

    Article  Google Scholar 

  135. Ehrman, R. N. et al. A scalable synthesis of adjuvanting antigen depots based on metal–organic frameworks. Chem. Sci. 15, 2731–2744 (2024).

    Article  Google Scholar 

  136. Lieschke, G. J. & Currie, P. D. Animal models of human disease: zebrafish swim into view. Nat. Rev. Genet. 8, 353–367 (2007).

    Article  Google Scholar 

  137. Chakraborty, C., Sharma, A. R., Sharma, G. & Lee, S.-S. Zebrafish: a complete animal model to enumerate the nanoparticle toxicity. J. Nanobiotechnol. 14, 65 (2016).

    Article  Google Scholar 

  138. Ruyra, À. et al. Synthesis, culture medium stability, and in vitro and in vivo zebrafish embryo toxicity of metal–organic framework nanoparticles. Chem. Eur. J. 21, 2508–2518 (2015).

    Article  Google Scholar 

  139. Rojas, S. et al. Pushing the limits on the intestinal crossing of metal–organic frameworks: an ex vivo and in vivo detailed study. ACS Nano 16, 5830–5838 (2022).

    Article  Google Scholar 

  140. Demir, E., Demir, F. T. & Marcos, R. in Nanotoxicology in Safety Assessment of Nanomaterials (eds Henriqueta, L. & Maria, J. S) Ch. 12, 275–301 (Springer International Publishing, 2022).

  141. Lopez-Chaves, C. et al. Gold nanoparticles: distribution, bioaccumulation and toxicity. In vitro and in vivo studies. Nanomedicine 14, 1–12 (2018).

    Article  Google Scholar 

  142. Foote, R. H. & Carney, E. W. The rabbit as a model for reproductive and developmental toxicity studies. Reprod. Toxicol. 14, 477–493 (2000).

    Article  Google Scholar 

  143. Ghasemi, A. & Zahediasl, S. Normality tests for statistical analysis: a guide for non-statisticians. Int. J. Endocrinol. Metab. 10, 486–489 (2012).

    Article  Google Scholar 

  144. Strasak, A. M., Zaman, Q., Pfeiffer, K. P., Göbel, G. & Ulmer, H. Statistical errors in medical research — a review of common pitfalls. Swiss Med. Wkly 137, 44–49 (2007).

    Google Scholar 

  145. Mishra, P., Pandey, C. M., Singh, U., Keshri, A. & Sabaretnam, M. Selection of appropriate statistical methods for data analysis. Ann. Card. Anaesth. 22, 297–301 (2019).

    Article  Google Scholar 

  146. Wu, M.-X. & Yang, Y.-W. Metal–organic framework (MOF)-based drug/cargo delivery and cancer therapy. Adv. Mater. 29, 1606134 (2017).

    Article  Google Scholar 

  147. Mallakpour, S., Nikkhoo, E. & Hussain, C. M. Application of MOF materials as drug delivery systems for cancer therapy and dermal treatment. Coord. Chem. Rev. 451, 214262 (2022).

    Article  Google Scholar 

  148. Saeb, M. R. et al. Metal–organic frameworks (MOFs) for cancer therapy. Materials 14, 7277 (2021).

    Article  ADS  Google Scholar 

  149. Jarai, B. M. et al. Evaluating UiO-66 metal–organic framework nanoparticles as acid-sensitive carriers for pulmonary drug delivery applications. ACS Appl. Mater. Interfaces 12, 38989–39004 (2020).

    Article  Google Scholar 

  150. Yang, L. et al. Pectin-coated iron-based metal–organic framework nanoparticles for enhanced foliar adhesion and targeted delivery of fungicides. ACS Nano 18, 6533–6594 (2024).

    Article  Google Scholar 

  151. Osorio-Toribio, G. et al. Controlled transdermal release of antioxidant ferulate by a porous Sc(III) MOF. iScience 23, 101156 (2020).

    Article  ADS  Google Scholar 

  152. Rojas, S. & Horcajada, P. Understanding the incorporation and release of salicylic acid in metal–organic frameworks for topical administration. Eur. J. Inorg. Chem. 2021, 1325–1331 (2021).

    Article  Google Scholar 

  153. Chen, J. et al. Current status and prospects of MOFs in controlled delivery of Pt anticancer drugs. Dalton Trans. 52, 6226–6238 (2023).

    Article  Google Scholar 

  154. Zhou, Y., Yang, T., Liang, K. & Chandrawati, R. Metal–organic frameworks for therapeutic gas delivery. Adv. Drug Deliv. Rev. 171, 199–214 (2021).

    Article  Google Scholar 

  155. Singh, R. et al. Potential of dual drug delivery systems: MOF as hybrid nanocarrier for dual drug delivery in cancer treatment. ChemistrySelect 7, e202201288 (2022).

    Article  Google Scholar 

  156. Ma, D. et al. Multifunctional nano MOF drug delivery platform in combination therapy. Eur. J. Med. Chem. 261, 115884 (2023).

    Article  Google Scholar 

  157. Yang, J. & Yang, Y.-W. Metal–organic framework-based cancer theranostic nanoplatforms. VIEW 1, e20 (2020).

    Article  Google Scholar 

  158. Shao, Y. et al. Engineering of upconverted metal–organic frameworks for near-infrared light-triggered combinational photodynamic/chemo-/immunotherapy against hypoxic tumors. J. Am. Chem. Soc. 142, 3939–3946 (2020).

    Article  Google Scholar 

  159. Fu, A., Tang, R., Hardie, J., Farkas, M. E. & Rotello, V. M. Promises and pitfalls of intracellular delivery of proteins. Bioconjugate Chem. 25, 1602–1608 (2014).

    Article  Google Scholar 

  160. Liang, K. et al. Biomimetic mineralization of metal–organic frameworks as protective coatings for biomacromolecules. Nat. Commun. 6, 7240 (2015).

    Article  ADS  Google Scholar 

  161. Yang, X. et al. Nanoscale ATP-responsive zeolitic imidazole framework-90 as a general platform for cytosolic protein delivery and genome editing. J. Am. Chem. Soc. 141, 3782–3786 (2019).

    Article  Google Scholar 

  162. Feng, Y. et al. Antibodies@MOFs: an in vitro protective coating for preparation and storage of biopharmaceuticals. Adv. Mater. 31, 1805148 (2019).

    Article  Google Scholar 

  163. Alsaiari, S. K. et al. Endosomal escape and delivery of CRISPR/Cas9 genome editing machinery enabled by nanoscale zeolitic imidazolate framework. J. Am. Chem. Soc. 140, 143–146 (2018). Using the in situ encapsulation methodology to deliver CRISPR–Cas9 gene editing machinery from a metal–organic framework.

    Article  Google Scholar 

  164. Chen, Y. et al. How can proteins enter the interior of a MOF? Investigation of cytochrome c translocation into a MOF consisting of mesoporous cages with microporous windows. J. Am. Chem. Soc. 134, 13188–13191 (2012).

    Article  Google Scholar 

  165. Wang, S. et al. DNA-functionalized metal–organic framework nanoparticles for intracellular delivery of proteins. J. Am. Chem. Soc. 141, 2215–2219 (2019).

    Article  Google Scholar 

  166. Chen, Y., Li, P., Modica, J. A., Drout, R. J. & Farha, O. K. Acid-resistant mesoporous metal–organic framework toward oral insulin delivery: protein encapsulation, protection, and release. J. Am. Chem. Soc. 140, 5678–5681 (2018).

    Article  Google Scholar 

  167. Thomas, C. E., Ehrhardt, A. & Kay, M. A. Progress and problems with the use of viral vectors for gene therapy. Nat. Rev. Genet. 4, 346–358 (2003).

    Article  Google Scholar 

  168. He, C., Lu, K., Liu, D. & Lin, W. Nanoscale metal–organic frameworks for the co-delivery of cisplatin and pooled siRNAs to enhance therapeutic efficacy in drug-resistant ovarian cancer cells. J. Am. Chem. Soc. 136, 5181–5184 (2014). Breakthrough development of methodologies to deliver short interfering RNAs using metal–organic frameworks.

    Article  Google Scholar 

  169. Peng, S. et al. Metal–organic frameworks for precise inclusion of single-stranded DNA and transfection in immune cells. Nat. Commun. 9, 1293 (2018).

    Article  ADS  Google Scholar 

  170. Teplensky, M. H. et al. A highly porous metal–organic framework system to deliver payloads for gene knockdown. Chem 5, 2926–2941 (2019).

    Article  Google Scholar 

  171. Cai, M. et al. Metal organic frameworks as drug targeting delivery vehicles in the treatment of cancer. Pharmaceutics 12, 232 (2020).

    Article  Google Scholar 

  172. Zhou, Z., Vázquez-González, M. & Willner, I. Stimuli-responsive metal–organic framework nanoparticles for controlled drug delivery and medical applications. Chem. Soc. Rev. 50, 4541–4563 (2021).

    Article  Google Scholar 

  173. Simon-Yarza, T. et al. A smart metal–organic framework nanomaterial for lung targeting. Angew. Chem. Int. Ed. 56, 15565–15569 (2017).

    Article  Google Scholar 

  174. Fernández, M., Javaid, F. & Chudasama, V. Advances in targeting the folate receptor in the treatment/imaging of cancers. Chem. Sci. 9, 790–810 (2018).

    Article  Google Scholar 

  175. Abánades Lázaro, I. et al. Mechanistic investigation into the selective anticancer cytotoxicity and immune system response of surface-functionalized, dichloroacetate-loaded, UiO-66 nanoparticles. ACS Appl. Mater. Interfaces 10, 5255–5268 (2018).

    Article  Google Scholar 

  176. Chen, D. et al. In vivo targeting and positron emission tomography imaging of tumor with intrinsically radioactive metal–organic frameworks nanomaterials. ACS Nano 11, 4315–4327 (2017).

    Article  Google Scholar 

  177. Alt, K. et al. Self-assembly of oriented antibody-decorated metal–organic framework nanocrystals for active-targeting applications. Adv. Mater. 34, 2106607 (2022).

    Article  Google Scholar 

  178. Cherkasov, V. R. et al. Antibody-directed metal–organic framework nanoparticles for targeted drug delivery. Acta Biomater. 103, 223–236 (2020).

    Article  Google Scholar 

  179. Haddad, S. et al. Design of a functionalized metal–organic framework system for enhanced targeted delivery to mitochondria. J. Am. Chem. Soc. 142, 6661–6674 (2020). Organelle targeted drug delivery by a surface-modified metal–organic framework.

    Article  Google Scholar 

  180. Chen, W.-H. et al. Stimuli-responsive nucleic acid-based polyacrylamide hydrogel-coated metal–organic framework nanoparticles for controlled drug release. Adv. Funct. Mater. 28, 1705137 (2018).

    Article  Google Scholar 

  181. Wang, H.-S. Metal–organic frameworks for biosensing and bioimaging applications. Coord. Chem. Rev. 349, 139–155 (2017).

    Article  ADS  Google Scholar 

  182. Taylor-Pashow, K. M. L., Della Rocca, J., Xie, Z., Tran, S. & Lin, W. Postsynthetic modifications of iron-carboxylate nanoscale metal−organic frameworks for imaging and drug delivery. J. Am. Chem. Soc. 131, 14261–14263 (2009).

    Article  Google Scholar 

  183. Liu, D., Huxford, R. C. & Lin, W. Phosphorescent nanoscale coordination polymers as contrast agents for optical imaging. Angew. Chem. Int. Ed. 50, 3696–3700 (2011).

    Article  Google Scholar 

  184. Nishiyabu, R. et al. Nanoparticles of adaptive supramolecular networks self-assembled from nucleotides and lanthanide ions. J. Am. Chem. Soc. 131, 2151–2158 (2009).

    Article  Google Scholar 

  185. Foucault-Collet, A. et al. Lanthanide near infrared imaging in living cells with Yb3+ nano metal organic frameworks. Proc. Natl Acad. Sci. USA 110, 17199–17204 (2013).

    Article  ADS  Google Scholar 

  186. Lan, G., Ni, K. & Lin, W. Nanoscale metal–organic frameworks for phototherapy of cancer. Coord. Chem. Rev. 379, 65–81 (2019).

    Article  Google Scholar 

  187. He, C., Lu, K. & Lin, W. Nanoscale metal–organic frameworks for real-time intracellular pH sensing in live cells. J. Am. Chem. Soc. 136, 12253–12256 (2014).

    Article  Google Scholar 

  188. Ma, Y. et al. Heterogeneous nano metal–organic framework fluorescence probe for highly selective and sensitive detection of hydrogen sulfide in living cells. Anal. Chem. 86, 11459–11463 (2014).

    Article  Google Scholar 

  189. Nagarkar, S. S., Saha, T., Desai, A. V., Talukdar, P. & Ghosh, S. K. Metal–organic framework based highly selective fluorescence turn-on probe for hydrogen sulphide. Sci. Rep. 4, 7053 (2014).

    Article  ADS  Google Scholar 

  190. Lu, Y., Yan, B. & Liu, J.-L. Nanoscale metal–organic frameworks as highly sensitive luminescent sensors for Fe2+ in aqueous solution and living cells. Chem. Commun. 50, 9969–9972 (2014).

    Article  Google Scholar 

  191. Wu, Y., Han, J., Xue, P., Xu, R. & Kang, Y. Nano metal–organic framework (NMOF)-based strategies for multiplexed microRNA detection in solution and living cancer cells. Nanoscale 7, 1753–1759 (2015).

    Article  ADS  Google Scholar 

  192. Carrillo-Carrión, C. Nanoscale metal–organic frameworks as key players in the context of drug delivery: evolution toward theranostic platforms. Anal. Bioanal. Chem. 412, 37–54 (2020).

    Article  Google Scholar 

  193. Xu, R. et al. Nanoscale metal–organic frameworks for ratiometric oxygen sensing in live cells. J. Am. Chem. Soc. 138, 2158–2161 (2016).

    Article  Google Scholar 

  194. Lan, G. et al. Multifunctional nanoscale metal–organic layers for ratiometric pH and oxygen sensing. J. Am. Chem. Soc. 141, 18964–18969 (2019).

    Article  Google Scholar 

  195. Gao, X. et al. RhB/UiO-66-N3 MOF-based ratiometric fluorescent detection and intracellular imaging of hydrogen sulfide. Sens. Actuators B 331, 129448 (2021).

    Article  Google Scholar 

  196. Yi, J.-T., Chen, T.-T., Huo, J. & Chu, X. Nanoscale zeolitic imidazolate framework-8 for ratiometric fluorescence imaging of microRNA in living cells. Anal. Chem. 89, 12351–12359 (2017).

    Article  Google Scholar 

  197. Ding, Z., Wang, C., Wang, S., Wu, L. & Zhang, X. Light-harvesting metal–organic framework nanoprobes for ratiometric fluorescence energy transfer-based determination of pH values and temperature. Microchim. Acta 186, 476 (2019).

    Article  Google Scholar 

  198. Xu, Z., Luo, T. & Lin, W. Nanoscale metal–organic layers for biomedical applications. Acc. Mater. Res. 2, 944–953 (2021).

    Article  Google Scholar 

  199. Ling, X. et al. Nanoscale metal–organic layers detect mitochondrial dysregulation and chemoresistance via ratiometric sensing of glutathione and pH. J. Am. Chem. Soc. 143, 1284–1289 (2021).

    Article  Google Scholar 

  200. Miller, S. E., Teplensky, M. H., Moghadam, P. Z. & Fairen-Jimenez, D. Metal–organic frameworks as biosensors for luminescence-based detection and imaging. Interface Focus 6, 20160027 (2016).

    Article  Google Scholar 

  201. Olorunyomi, J. F., Geh, S. T., Caruso, R. A. & Doherty, C. M. Metal–organic frameworks for chemical sensing devices. Mater. Horiz. 8, 2387–2419 (2021).

    Article  Google Scholar 

  202. Ho, T.-L., Ho, H. C. & Hamilton, L. D. Biochemical significance of the hard and soft acids and bases principle. Chem.-Biol. Interact. 23, 65–84 (1978).

    Article  Google Scholar 

  203. Schwöbel, J. A. H. et al. Measurement and estimation of electrophilic reactivity for predictive toxicology. Chem. Rev. 111, 2562–2596 (2011).

    Article  Google Scholar 

  204. Bunzen, H. & Jirák, D. Recent advances in metal–organic frameworks for applications in magnetic resonance imaging. ACS Appl. Mater. Interfaces 14, 50445–50462 (2022).

    Article  Google Scholar 

  205. Böll, K., Zimpel, A., Dietrich, O., Wuttke, S. & Peller, M. Clinically approved MRI contrast agents as imaging labels for a porous iron-based MOF nanocarrier: a systematic investigation in a clinical MRI setting. Adv. Ther. 3, 1900126 (2020).

    Article  Google Scholar 

  206. Jia, M. et al. Grafting of Gd-DTPA onto MOF-808 to enhance MRI performance for guiding photothermal therapy. J. Mater. Chem. B 9, 8631–8638 (2021).

    Article  Google Scholar 

  207. Sene, S. et al. Maghemite-nanoMIL-100(Fe) bimodal nanovector as a platform for image-guided therapy. Chem 3, 303–322 (2017).

    Article  Google Scholar 

  208. Zhao, H.-X. et al. Theranostic metal–organic framework core–shell composites for magnetic resonance imaging and drug delivery. Chem. Sci. 7, 5294–5301 (2016).

    Article  Google Scholar 

  209. Wang, G. D., Chen, H., Tang, W., Lee, D. & Xie, J. Gd and Eu co-doped nanoscale metal–organic framework as a T1–T2 dual-modal contrast agent for magnetic resonance imaging. Tomography 2, 179–187 (2016).

    Article  Google Scholar 

  210. Dehghani, S. et al. The effect of size and aspect ratio of Fe-MIL-88B-NH2 metal–organic frameworks on their relaxivity and contrast enhancement properties in MRI: in vitro and in vivo studies. J. Nanopart. Res. 20, 278 (2018).

    Article  ADS  Google Scholar 

  211. Peller, M., Böll, K., Zimpel, A. & Wuttke, S. Metal–organic framework nanoparticles for magnetic resonance imaging. Inorg. Chem. Front. 5, 1760–1779 (2018).

    Article  Google Scholar 

  212. deKrafft, K. E. et al. Iodinated nanoscale coordination polymers as potential contrast agents for computed tomography. Angew. Chem. Int. Ed. 48, 9901–9904 (2009).

    Article  Google Scholar 

  213. deKrafft, K. E., Boyle, W. S., Burk, L. M., Zhou, O. Z. & Lin, W. Zr- and Hf-based nanoscale metal–organic frameworks as contrast agents for computed tomography. J. Mater. Chem. 22, 18139–18144 (2012).

    Article  Google Scholar 

  214. Zhang, T. et al. BODIPY-containing nanoscale metal–organic frameworks as contrast agents for computed tomography. J. Mater. Chem. B 5, 2330–2336 (2017).

    Article  Google Scholar 

  215. Wang, C. et al. Synergistic assembly of heavy metal clusters and luminescent organic bridging ligands in metal–organic frameworks for highly efficient X-ray scintillation. J. Am. Chem. Soc. 136, 6171–6174 (2014).

    Article  Google Scholar 

  216. Xu, Z. et al. Monte Carlo simulation-guided design of a thorium-based metal–organic framework for efficient radiotherapy–radiodynamic therapy. Angew. Chem. Int. Ed. 61, e202208685 (2022).

    Article  Google Scholar 

  217. Lu, K. et al. Low-dose X-ray radiotherapy–radiodynamic therapy via nanoscale metal–organic frameworks enhances checkpoint blockade immunotherapy. Nat. Biomed. Eng. 2, 600–610 (2018). Multimodal metal–organic framework therapy combining radiotherapy–radiodynamic therapy with delivery of immunotherapeutics.

    Article  Google Scholar 

  218. Shang, W. et al. Core–shell gold nanorod@metal–organic framework nanoprobes for multimodality diagnosis of glioma. Adv. Mater. 29, 1604381 (2017).

    Article  Google Scholar 

  219. Liu, Y. et al. In situ polymerization on nanoscale metal–organic frameworks for enhanced physiological stability and stimulus-responsive intracellular drug delivery. Biomaterials 218, 119365 (2019).

    Article  Google Scholar 

  220. Liu, Y. et al. Novel CD-MOF NIR-II fluorophores for gastric ulcer imaging. Chin. Chem. Lett. 32, 3061–3065 (2021).

    Article  Google Scholar 

  221. Cai, W. et al. Engineering phototheranostic nanoscale metal–organic frameworks for multimodal imaging-guided cancer therapy. ACS Appl. Mater. Interfaces 9, 2040–2051 (2017).

    Article  Google Scholar 

  222. Zhang, D. et al. Self-quenched metal–organic particles as dual-mode therapeutic agents for photoacoustic imaging-guided second near-infrared window photochemotherapy. ACS Appl. Mater. Interfaces 10, 25203–25212 (2018).

    Article  Google Scholar 

  223. Zeng, J.-Y., Zhang, M.-K., Peng, M.-Y., Gong, D. & Zhang, X.-Z. Porphyrinic metal–organic frameworks coated gold nanorods as a versatile nanoplatform for combined photodynamic/photothermal/chemotherapy of tumor. Adv. Funct. Mater. 28, 1705451 (2018).

    Article  Google Scholar 

  224. Chen, X. et al. Facile synthesis of polypyrrole@metal–organic framework core–shell nanocomposites for dual-mode imaging and synergistic chemo-photothermal therapy of cancer cells. J. Mater. Chem. B 5, 1772–1778 (2017).

    Article  ADS  Google Scholar 

  225. Freedman, L. P., Cockburn, I. M. & Simcoe, T. S. The economics of reproducibility in preclinical research. PLoS Biol. 13, e1002165 (2015).

    Article  Google Scholar 

  226. Leroux, J.-C. Editorial: drug delivery: too much complexity, not enough reproducibility? Angew. Chem. Int. Ed. 56, 15170–15171 (2017).

    Article  Google Scholar 

  227. Dirnagl, U., Duda, G. N., Grainger, D. W., Reinke, P. & Roubenoff, R. Reproducibility, relevance and reliability as barriers to efficient and credible biomedical technology translation. Adv. Drug Deliv. Rev. 182, 114118 (2022).

    Article  Google Scholar 

  228. Bostrom, H. et al. How reproducible is the synthesis of Zr–porphyrin metal–organic frameworks? An interlaboratory study. Adv. Mater. 36, 2304832 (2024). An interlaboratory study showing the difficulty in reproducing previously validated metal–organic framework synthetic protocols.

    Article  Google Scholar 

  229. Hughes, P., Marshall, D., Reid, Y., Parkes, H. & Gelber, C. The costs of using unauthenticated, over-passaged cell lines: how much more data do we need. BioTechniques 43, 575–586 (2007).

    Article  Google Scholar 

  230. Riss, T. L. et al. in Assay Guidance Manual (eds Markossian, S., Grossman, A. & Brimacombe, K.) 403–427 (Eli Lilly & Company and the National Center for Advancing Translational Sciences, 2013).

  231. Bimler, D. Better living through coordination chemistry: a descriptive study of a prolific papermill that combines crystallography and medicine. Res. Sq. https://doi.org/10.21203/rs.3.rs-1537438/v1 (2022).

    Article  Google Scholar 

  232. Horbach, S. P. J. M. & Halffman, W. The ghosts of HeLa: how cell line misidentification contaminates the scientific literature. PLoS ONE 12, e0186281 (2017).

    Article  Google Scholar 

  233. Evans, J. D., Bon, V., Senkovska, I. & Kaskel, S. A universal standard archive file for adsorption data. Langmuir 37, 4222–4226 (2021).

    Article  Google Scholar 

  234. Forgan, R. S. Reproducibility in research into metal–organic frameworks in nanomedicine. Commun. Mater. 5, 46 (2024).

    Article  Google Scholar 

  235. Lu, K. et al. Chlorin-based nanoscale metal–organic framework systemically rejects colorectal cancers via synergistic photodynamic therapy and checkpoint blockade immunotherapy. J. Am. Chem. Soc. 138, 12502–12510 (2016).

    Article  Google Scholar 

  236. Nash, G. T. et al. Nanoscale metal–organic layer isolates phthalocyanines for efficient mitochondria-targeted photodynamic therapy. J. Am. Chem. Soc. 143, 2194–2199 (2021).

    Article  Google Scholar 

  237. Luo, T. et al. Nanoscale metal–organic framework confines zinc-phthalocyanine photosensitizers for enhanced photodynamic therapy. J. Am. Chem. Soc. 143, 13519–13524 (2021).

    Article  Google Scholar 

  238. Luo, T. et al. Nanoscale metal–organic frameworks stabilize bacteriochlorins for type I and type II photodynamic therapy. J. Am. Chem. Soc. 142, 7334–7339 (2020).

    Article  Google Scholar 

  239. Ni, K. et al. Nanoscale metal–organic frameworks enhance radiotherapy to potentiate checkpoint blockade immunotherapy. Nat. Commun. 9, 2351 (2018).

    Article  ADS  Google Scholar 

  240. Ni, K., Luo, T., Nash, G. T. & Lin, W. Nanoscale metal–organic frameworks for cancer immunotherapy. Acc. Chem. Res. 53, 1739–1748 (2020).

    Article  Google Scholar 

  241. Ni, K. et al. Nanoscale metal–organic framework co-delivers TLR-7 agonists and anti-CD47 antibodies to modulate macrophages and orchestrate cancer immunotherapy. J. Am. Chem. Soc. 142, 12579–12584 (2020).

    Article  Google Scholar 

  242. Ni, K. et al. Nanoscale metal–organic frameworks for X-ray activated in situ cancer vaccination. Sci. Adv. 6, eabb5223 (2020).

    Article  ADS  Google Scholar 

  243. Luo, T. et al. A 2D nanoradiosensitizer enhances radiotherapy and delivers STING agonists to potentiate cancer immunotherapy. Adv. Mater. 34, 2110588 (2022).

    Article  Google Scholar 

  244. Wijesundara, Y. H., Howlett, T. S., Kumari, S. & Gassensmith, J. J. The promise and potential of metal–organic frameworks and covalent organic frameworks in vaccine nanotechnology. Chem. Rev. 124, 3013–3036 (2024). A comprehensive overview of the potential of metal–organic frameworks in immunology.

    Article  Google Scholar 

  245. Miao, Y.-B. et al. Engineering a nanoscale Al-MOF-armored antigen carried by a ‘Trojan Horse’-like platform for oral vaccination to induce potent and long-lasting immunity. Adv. Funct. Mater. 29, 1904828 (2019).

    Article  Google Scholar 

  246. Kumari, S. et al. Biolistic delivery of liposomes protected in metal–organic frameworks. Proc. Natl Acad. Sci. USA 120, e2218247120 (2023).

    Article  Google Scholar 

  247. Wijesundara, Y. H. et al. Carrier gas triggered controlled biolistic delivery of DNA and protein therapeutics from metal–organic frameworks. Chem. Sci. 13, 13803–13814 (2022).

    Article  Google Scholar 

  248. Pouyanfar, N., Ahmadi, M., Ayyoubzadeh, S. M. & Ghorbani-Bidkorpeh, F. Drug delivery system tailoring via metal–organic framework property prediction using machine learning: a disregarded approach. Mater. Today Commun. 38, 107938 (2024).

    Article  Google Scholar 

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Acknowledgements

A.E., D.F.-J. and R.S.F. thank the EPSRC for funding (EP/S009000/1). R.G. acknowledges funding from ANR-20-CE19-0020. I.A.L. and M.G.-M. thank financial support from LCF/BQ/PR23/11980041 and MCIN/AEI/10.13039/501100011033 (TED2021-132729A-I00), respectively. T.L. and W.L. thank the National Cancer Institute for funding (1R01CA253655).

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Authors and Affiliations

  1. Institute of Molecular Science (ICMol), University of Valencia, Valencia, Spain

    Isabel Abánades Lázaro & Mónica Giménez-Marqués

  2. The Adsorption & Advanced Materials Laboratory (A2ML), Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK

    Xu Chen & David Fairen-Jimenez

  3. Institut des Sciences Moléculaires d’Orsay, UMR 8216 CNRS, Paris Saclay University, Paris, France

    Mengli Ding & Ruxandra Gref

  4. School of Chemistry, University of Glasgow, Glasgow, UK

    Arvin Eskandari & Ross S. Forgan

  5. Department of Chemistry, University of Chicago, Chicago, IL, USA

    Wenbin Lin & Taokun Luo

Authors
  1. Isabel Abánades Lázaro
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  2. Xu Chen
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  3. Mengli Ding
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  4. Arvin Eskandari
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  5. David Fairen-Jimenez
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  6. Mónica Giménez-Marqués
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  7. Ruxandra Gref
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  8. Wenbin Lin
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  9. Taokun Luo
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  10. Ross S. Forgan
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Contributions

Introduction (R.S.F.); Experimentation (I.A.L., M.G.-M., M.D., R.G. and A.E.); Results (R.G., M.D., I.A.L., M.G.-M., A.E., X.C. and D.F.-J.); Applications (W.L., T.L., R.G. and M.D.); Reproducibility and data deposition (R.S.F.); Limitations and optimizations (R.S.F., W.L. and T.L.); Outlook (R.S.F., W.L. and T.L.); Overview of the Primer (R.S.F. and A.E.).

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Correspondence to Ross S. Forgan.

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Glossary

Activation

The process of removing unreacted reagents and/or solvents from the pores of a synthesized metal–organic framework to maximize the available porosity and molecular storage capacity.

Burst release

Rapid release of cargo from a drug delivery system.

Coordinative functionalization

Postsynthetic modification involving formation of a coordinative bond between the metal–organic framework and the functionality, typically occurring at the inorganic secondary building unit.

Covalent conjugation

Postsynthetic modification involving formation of a covalent bond between the metal–organic framework and the functionality, typically occurring at the organic linker.

Defect loading

The process of loading a drug within a metal–organic framework by deliberately incorporating it as a charge-balancing defect during synthesis. This requires the drug to have a coordinating unit to allow it to replace a linker at the secondary building unit during metal–organic framework synthesis.

Drug delivery systems

Also known as drug delivery devices and drug delivery vectors. A formulation or device that enhances the uptake and efficacy of a specific drug within the body.

Drug loading

A measure of the loading capacity of a drug delivery system that is defined as the mass of the drug divided by the mass of the carrier and converted to a percentage. Note that this measure can result in >100% drug loading values and is distinct from the alternative wt% loading measure.

Encapsulation efficiency

A measure of the uptake efficiency of a drug delivery system for a specific analyte, which is calculated as the percentage of drug encapsulated from the total amount of drug contacted with the drug delivery system in a loading experiment.

Hard inorganic systems

A classification of drug delivery systems that includes inorganic systems such as noble metal nanoparticles, mesoporous silica, layered double hydroxides and metal–organic frameworks that are characterized by high drug loading values but often poorer biocompatibility and clearance.

Modulated self-assembly

Synthetic protocols for metal–organic frameworks in which additives are used to control pH and coordinative equilibria during self-assembly and so influence phase formation and/or metal–organic framework physical properties such as size, porosity and defectivity.

Organic linkers

Multitopic organic ligands used to construct metal–organic frameworks, typically carboxylates, phosphonates or N-donor heterocycles.

Pearson’s hard and soft acids and bases principle

Qualitatively, hard Lewis acids will be more stabilized by hard Lewis bases, and similarly soft Lewis acids will be more stabilized by soft Lewis bases, which can explain stability (and selectivity) of metal coordination chemistry.

Secondary building unit

(SBU). Inorganic metal ions or clusters that connect the organic linkers into the metal–organic framework structure.

Soft organic systems

A classification of drug delivery systems that includes organic, often polymer-based systems, such as liposomes or lipid nanoparticles, that are characterized by excellent biocompatibility and clearance but often low drug loading values.

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Abánades Lázaro, I., Chen, X., Ding, M. et al. Metal–organic frameworks for biological applications. Nat Rev Methods Primers 4, 42 (2024). https://doi.org/10.1038/s43586-024-00320-8

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