In this section
@article{Cryer:2019:10.1021/acsami.9b02986,
author = {Cryer, AM and Chan, C and Eftychidou, A and Maksoudian, C and Mahesh, M and Tetley, TD and Spivey, AC and Thorley, AJ},
doi = {10.1021/acsami.9b02986},
journal = {ACS Applied Materials and Interfaces},
pages = {16336--16346},
title = {Tyrosine kinase inhibitor gold nanoconjugates for the treatment of non-small cell lung cancer},
url = {http://dx.doi.org/10.1021/acsami.9b02986},
volume = {11},
year = {2019}
}
TY - JOUR
AB - 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 pro-inflammatory cytokines when compared to free drug, demonstrating the biocompatibility of our formulation. This study provides a new platform for the development of non-traditional 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.
AU - Cryer,AM
AU - Chan,C
AU - Eftychidou,A
AU - Maksoudian,C
AU - Mahesh,M
AU - Tetley,TD
AU - Spivey,AC
AU - Thorley,AJ
DO - 10.1021/acsami.9b02986
EP - 16346
PY - 2019///
SN - 1944-8244
SP - 16336
TI - Tyrosine kinase inhibitor gold nanoconjugates for the treatment of non-small cell lung cancer
T2 - ACS Applied Materials and Interfaces
UR - http://dx.doi.org/10.1021/acsami.9b02986
UR - https://www.ncbi.nlm.nih.gov/pubmed/30986026
UR - http://hdl.handle.net/10044/1/71402
VL - 11
ER -
Email: a.c.spivey@imperial.ac.uk
Skype: alan.spivey
Tel & Fax: +44 (0)20 75945841
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