دورية أكاديمية
أعرض في EDS

Circumventing Physicochemical Barriers of Cyclometalated Gold(III) Dithiocarbamate Complexes with Protein-Based Nanoparticle Delivery to Enhance Anticancer Activity.

التفاصيل البيبلوغرافية
العنوان: Circumventing Physicochemical Barriers of Cyclometalated Gold(III) Dithiocarbamate Complexes with Protein-Based Nanoparticle Delivery to Enhance Anticancer Activity.
المؤلفون: Arojojoye AS; Department of Chemistry, University of Kentucky, Lexington Kentucky 40506, United States., Walker B; Department of Chemistry, University of Kentucky, Lexington Kentucky 40506, United States., Dawahare JC; Department of Chemistry, University of Kentucky, Lexington Kentucky 40506, United States., Afrifa MAO; Department of Biomedical Engineering, University of Kentucky, Lexington Kentucky 40506, United States., Parkin S; Department of Chemistry, University of Kentucky, Lexington Kentucky 40506, United States., Awuah SG; Department of Chemistry, University of Kentucky, Lexington Kentucky 40506, United States.; Center for Pharmaceutical Research and Innovation and Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington Kentucky 40536, United States.; Markey Cancer Center, University of Kentucky, Lexington Kentucky 40536, United States.
المصدر: ACS applied materials & interfaces [ACS Appl Mater Interfaces] 2023 Sep 20; Vol. 15 (37), pp. 43607-43620. Date of Electronic Publication: 2023 Sep 12.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 101504991 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1944-8252 (Electronic) Linking ISSN: 19448244 NLM ISO Abbreviation: ACS Appl Mater Interfaces Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Chemical Society
مواضيع طبية MeSH: Gold* , Nanoparticles*, Serum Albumin, Bovine ; Biological Availability ; Drug Delivery Systems
مستخلص: Optimizing the bioavailability of drug candidates is crucial to successful drug development campaigns, especially for metal-derived chemotherapeutic agents. Nanoparticle delivery strategies can be deployed to overcome physicochemical limitations associated with drugs to improve bioavailability, pharmacokinetics, efficacy, and minimize toxicity. Biodegradable albumin nanoconstructs offer pragmatic solutions for drug delivery of metallodrugs with translational benefits in the clinic. In this work, we explored a logical approach to investigate and resolve the physicochemical drawbacks of gold(III) complexes with albumin nanoparticle delivery to improve solubility, enhance intracellular accumulation, circumvent premature deactivation, and enhance anticancer activity. We synthesized and characterized stable gold(III) dithiocarbamate complexes with a variable degree of cyclometalation such as phenylpyridine (C^N) or biphenyl (C^C) Au(III) framework and different alkyl chain lengths. We noted that extended alkyl chain lengths impaired the solubility of these complexes in biological media, thus adversely impacting potency. Encapsulation of these complexes in bovine serum albumin (BSA) reversed solubility limitations and improved cancer cytotoxicity by ∼25-fold. Further speciation and mechanism of action studies demonstrate the stability of the compounds and alteration of mitochondria bioenergetics, respectively. We postulate that this nanodelivery strategy is a relevant approach for translational small-molecule gold drug delivery.
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معلومات مُعتمدة: P20 GM103436 United States GM NIGMS NIH HHS; P20 GM130456 United States GM NIGMS NIH HHS; P30 CA177558 United States CA NCI NIH HHS; R01 CA258421 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: bovine serum albumin; cyclometalation; dithiocarbamate; encapsulation; gold(III); nanoparticles; stability
المشرفين على المادة: 7440-57-5 (Gold)
27432CM55Q (Serum Albumin, Bovine)
تواريخ الأحداث: Date Created: 20230912 Date Completed: 20230922 Latest Revision: 20240921
رمز التحديث: 20240921
مُعرف محوري في PubMed: PMC11264193
DOI: 10.1021/acsami.3c10025
PMID: 37698293
قاعدة البيانات: MEDLINE
الوصف
تدمد:1944-8252
DOI:10.1021/acsami.3c10025