NDLI: A multi-functional PEGylated gold(iii) compound: potent anti-cancer properties and self-assembly into nanostructures for drug co-delivery

Content Provider	Royal Society of Chemistry (RSC)
Author	Che, Chi-Ming Huang, Yanyu Lok, Chun-Nam Tong, Ka-Chung Fung, Sin-Ki Wan, Pui-Ki Chung, Clive Yik-Sham Chen, Tianfeng
Copyright Year	2017
Abstract	Gold(III) porphyrin–PEG conjugates [Au(TPP–COO–PEG5000–OCH3)]Cl (1) and [Au(TPP–CONH–PEG5000–OCH3)]Cl (2) have been synthesized and characterized. Based on the amphiphilic character of the conjugates, they were found to undergo self-assembly into nanostructures with size 120–200 nm and this did not require the presence of other surfactants or components for nano-assembly, unlike most conventional drug nano-formulations. With a readily hydrolyzable ester linkage, chemotherapeutic [Au(TPP–COOH)]+ exhibited triggered release from the conjugate 1 in acidic buffer solution as well as in vitro and in vivo without the formation of toxic side products. The nanostructures of 1 showed higher cellular uptake into cancer cells compared to non-tumorigenic cells, owing to their energy-dependent uptake mechanism. This, together with a generally higher metabolic rate and more acidic nature of cancer cells which can lead to faster hydrolysis of the ester bond, afforded 1 with excellent selectivity in killing cancer cells compared with non-tumorigenic cells in vitro. This was corroborated by fluorescence microscopy imaging and flow cytometric analysis of co-culture model of colon cancer (HCT116) and normal colon (NCM460) cells. In vivo experiments showed that treatment of nude mice bearing HCT116 xenografts with 1 resulted in significant inhibition of tumor growth and, more importantly, minimal systemic toxicity as revealed by histopathological analysis of tissue sections and blood biochemisty. The latter is explained by a lower accumulation of 1 in organs of treated mice at its effective dosage, as compared to that of other gold(III) porphyrin complexes. Co-assembly of 1 and doxorubicin resulted in encapsulation of doxorubicin by the nanostructures of 1. The nanocomposites demonstrated a strong synergism on killing cancer cells and could overcome efflux pump-mediated drug-resistance in a doxorubicin-resistant ovarian cancer cell line (A2780adr) which was found in cells incubated with doxorubicin alone. Also, the nanocomposites accumulated more slowly in non-tumorigenic cells, resulting in a lower toxicity toward non-tumorigenic cells. These results indicate the potential application of 1 not only as an anti-cancer agent but also as a nanoscale drug carrier for chemotherapy.
Starting Page	1942
Ending Page	1953
Page Count	12
File Format	HTM / HTML PDF
ISSN	20416520
Volume Number	8
Issue Number	3
Journal	Chemical Science
DOI	10.1039/c6sc03210a
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Subscribed
Subject Keyword	Flow cytometry Colorectal cancer Buffer solution Metabolism Nude mouse Doxorubicin Ovarian cancer Hydrolysis Ester Self-assembly Chemotherapy Microscopy Porphyrin Covalent bond Amphiphile Cancer NCI-60
Content Type	Text
Resource Type	Article
Subject	Chemistry

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