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Tyrosine Kinase Inhibitor Gold Nanoconjugates for the Treatment of Non-Small Cell Lung Cancer.

Cryer, Alexander M and Chan, Cheuk and Eftychidou, Anastasia and Maksoudian, Christy and Mahesh, Mohan and Tetley, Teresa D and Spivey, Alan C and Thorley, Andrew J (2019) Tyrosine Kinase Inhibitor Gold Nanoconjugates for the Treatment of Non-Small Cell Lung Cancer. ACS applied materials & interfaces, 11 (18). pp. 16336-16346. ISSN 1944-8252

Abstract

Gold nanoparticles (AuNPs) have emerged as promising drug delivery candidates that can be leveraged for cancer therapy. Lung cancer (LC) is a heterogeneous disease that imposes a significant burden on society, with an unmet need for new therapies. Chemotherapeutic drugs such as afatinib (Afb), which is clinically approved for the treatment of epidermal growth factor receptor positive LC, is hydrophobic and has low bioavailability leading to spread around the body, causing severe side effects. Herein, we present a novel afatinib-AuNP formulation termed Afb-AuNPs, with the aim of improving drug efficacy and biocompatibility. This was achieved by synthesis of an alkyne-bearing Afb derivative and reaction with azide-functionalized lipoic acid using copper-catalyzed click chemistry, then conjugation to AuNPs via alkylthiol-gold bond formation. The Afb-AuNPs were found to possess up to 3.7-fold increased potency when administered to LC cells in vitro and were capable of significantly inhibiting cancer cell proliferation, as assessed by MTT assay and electric cell-substrate impedance sensing, respectively. Furthermore, when exposed to Afb-AuNPs, human alveolar epithelial type I-like cells, a model of the healthy lung epithelium, maintained viability and were found to release less proinflammatory cytokines when compared to free drug, demonstrating the biocompatibility of our formulation. This study provides a new platform for the development of nontraditional AuNP conjugates which can be applied to other molecules of therapeutic or diagnostic utility, with potential to be combined with photothermal therapy in other cancers.

Item Type: Article
Date Deposited: 31 Aug 2019 00:45
Last Modified: 31 Aug 2019 00:45
URI: https://oak.novartis.com/id/eprint/40786

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