Design of a Functionalized Metal–Organic Framework System for Enhanced Targeted Delivery to Mitochondria
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Título: | Design of a Functionalized Metal–Organic Framework System for Enhanced Targeted Delivery to Mitochondria |
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Autor/es: | Haddad, Salame | Abánades Lázaro, Isabel | Fantham, Marcus | Mishra, Ajay | Silvestre-Albero, Joaquín | Osterrieth, Johannes W. M. | Kaminski Schierle, Gabriele S. | Kaminski, Clemens F. | Forgan, Ross S. | Fairen-Jimenez, David |
Grupo/s de investigación o GITE: | Materiales Avanzados |
Centro, Departamento o Servicio: | Universidad de Alicante. Departamento de Química Inorgánica | Universidad de Alicante. Instituto Universitario de Materiales |
Palabras clave: | Mitochondria | Metal–organic framework | Enhanced targeted delivery |
Área/s de conocimiento: | Química Inorgánica |
Fecha de publicación: | 17-mar-2020 |
Editor: | American Chemical Society |
Cita bibliográfica: | Journal of the American Chemical Society. 2020, 142(14): 6661-6674. doi:10.1021/jacs.0c00188 |
Resumen: | Mitochondria play a key role in oncogenesis and constitute one of the most important targets for cancer treatments. Although the most effective way to deliver drugs to mitochondria is by covalently linking them to a lipophilic cation, the in vivo delivery of free drugs still constitutes a critical bottleneck. Herein, we report the design of a mitochondria-targeted metal–organic framework (MOF) that greatly increases the efficacy of a model cancer drug, reducing the required dose to less than 1% compared to the free drug and ca. 10% compared to the nontargeted MOF. The performance of the system is evaluated using a holistic approach ranging from microscopy to transcriptomics. Super-resolution microscopy of MCF-7 cells treated with the targeted MOF system reveals important mitochondrial morphology changes that are clearly associated with cell death as soon as 30 min after incubation. Whole transcriptome analysis of cells indicates widespread changes in gene expression when treated with the MOF system, specifically in biological processes that have a profound effect on cell physiology and that are related to cell death. We show how targeting MOFs toward mitochondria represents a valuable strategy for the development of new drug delivery systems. |
Patrocinador/es: | This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (NanoMOFdeli), ERC-2016-COG 726380, and (SCoTMOF), ERC-2015-STG-677289. D.F.-J. and R.S.F. thank the Royal Society for funding through University Research Fellowships. C.F.K. acknowledges funding from the UK Engineering and Physical Sciences Research Council, EPSRC (grants EP/L015889/1 and EP/H018301/1), the Wellcome Trust (grants 3-3249/Z/16/Z and 089703/Z/09/Z) and the UK Medical Research Council, MRC (grants MR/K015850/1 and MR/K02292X/1), and Infinitus (China) Ltd. We thank EPSRC (grant EP/S009000/1). |
URI: | http://hdl.handle.net/10045/105268 |
ISSN: | 0002-7863 (Print) | 1520-5126 (Online) |
DOI: | 10.1021/jacs.0c00188 |
Idioma: | eng |
Tipo: | info:eu-repo/semantics/article |
Derechos: | This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. |
Revisión científica: | si |
Versión del editor: | https://doi.org/10.1021/jacs.0c00188 |
Aparece en las colecciones: | INV - LMA - Artículos de Revistas Investigaciones financiadas por la UE |
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