دورية أكاديمية
أعرض في EDS

Design of a Functionalized Metal-Organic Framework System for Enhanced Targeted Delivery to Mitochondria.

التفاصيل البيبلوغرافية
العنوان: Design of a Functionalized Metal-Organic Framework System for Enhanced Targeted Delivery to Mitochondria.
المؤلفون: Haddad S; Adsorption & Advanced Materials Laboratory (AAML), Department of Chemical Engineering & Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge CB3 0AS, U.K., Abánades Lázaro I; WestCHEM School of Chemistry, University of Glasgow, Joseph Black Building, University Avenue, Glasgow G12 8QQ, U.K., Fantham M; Laser Analytics Group, Department of Chemical Engineering & Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge CB3 0AS, U.K., Mishra A; Cambridge Infinitus Research Centre, Department of Chemical Engineering & Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge CB3 0AS, U.K., Silvestre-Albero J; Laboratorio de Materiales Avanzados, Departamento de Quı́mica Inorgánica-Instituto Universitario de Materiales, Universidad de Alicante, E-03690 San Vicente del Raspeig, Spain., Osterrieth JWM; Adsorption & Advanced Materials Laboratory (AAML), Department of Chemical Engineering & Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge CB3 0AS, U.K., Kaminski Schierle GS; Molecular Neuroscience Group, Department of Chemical Engineering & Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge CB3 0AS, U.K., Kaminski CF; Laser Analytics Group, Department of Chemical Engineering & Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge CB3 0AS, U.K., Forgan RS; WestCHEM School of Chemistry, University of Glasgow, Joseph Black Building, University Avenue, Glasgow G12 8QQ, U.K., Fairen-Jimenez D; Adsorption & Advanced Materials Laboratory (AAML), Department of Chemical Engineering & Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge CB3 0AS, U.K.
المصدر: Journal of the American Chemical Society [J Am Chem Soc] 2020 Apr 08; Vol. 142 (14), pp. 6661-6674. Date of Electronic Publication: 2020 Mar 27.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 7503056 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-5126 (Electronic) Linking ISSN: 00027863 NLM ISO Abbreviation: J Am Chem Soc Subsets: MEDLINE
أسماء مطبوعة: Publication: Washington, DC : American Chemical Society
Original Publication: Easton, Pa. [etc.]
مواضيع طبية MeSH: Drug Delivery Systems/*methods , Metal-Organic Frameworks/*metabolism , Mitochondria/*metabolism, Humans
مستخلص: 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.
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معلومات مُعتمدة: MR/K02292X/1 United Kingdom MRC_ Medical Research Council; 203249/Z/16/Z United Kingdom WT_ Wellcome Trust; 3-3249/Z/16/Z United Kingdom WT_ Wellcome Trust; MR/K015850/1 United Kingdom MRC_ Medical Research Council; 089703/Z/09/Z United Kingdom WT_ Wellcome Trust; United Kingdom WT_ Wellcome Trust
المشرفين على المادة: 0 (Metal-Organic Frameworks)
تواريخ الأحداث: Date Created: 20200318 Date Completed: 20210415 Latest Revision: 20231103
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC7146860
DOI: 10.1021/jacs.0c00188
PMID: 32182066
قاعدة البيانات: MEDLINE
الوصف
تدمد:1520-5126
DOI:10.1021/jacs.0c00188