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

TitleA multi-functional PEGylated gold(III) compound: potent anti-cancer properties and self-assembly into nanostructures for drug co-delivery
Authors
Issue Date2017
PublisherRoyal Society of Chemistry. The Journal's web site is located at http://www.rsc.org/publishing/journals/sc/About.asp
Citation
Chemical Science, 2017, v. 8 n. 3, p. 1942-1953 How to Cite?
AbstractGold(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.
Persistent Identifierhttp://hdl.handle.net/10722/242992
ISSN
2019 Impact Factor: 9.346
2015 SCImago Journal Rankings: 4.974
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChung, CYS-
dc.contributor.authorFung, SK-
dc.contributor.authorTong, KC-
dc.contributor.authorWan, PK-
dc.contributor.authorLok, CN-
dc.contributor.authorHuang, Y-
dc.contributor.authorChen, T-
dc.contributor.authorChe, CM-
dc.date.accessioned2017-08-25T02:48:25Z-
dc.date.available2017-08-25T02:48:25Z-
dc.date.issued2017-
dc.identifier.citationChemical Science, 2017, v. 8 n. 3, p. 1942-1953-
dc.identifier.issn2041-6520-
dc.identifier.urihttp://hdl.handle.net/10722/242992-
dc.description.abstractGold(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.-
dc.languageeng-
dc.publisherRoyal Society of Chemistry. The Journal's web site is located at http://www.rsc.org/publishing/journals/sc/About.asp-
dc.relation.ispartofChemical Science-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleA multi-functional PEGylated gold(III) compound: potent anti-cancer properties and self-assembly into nanostructures for drug co-delivery-
dc.typeArticle-
dc.identifier.emailChung, YSC: cyschung@hku.hk-
dc.identifier.emailLok, CN: cnlok@hku.hk-
dc.identifier.emailChe, CM: chemhead@hku.hk-
dc.identifier.authorityLok, CN=rp00752-
dc.identifier.authorityChe, CM=rp00670-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1039/C6SC03210A-
dc.identifier.pmid28451309-
dc.identifier.pmcidPMC5384453-
dc.identifier.scopuseid_2-s2.0-85014058615-
dc.identifier.hkuros273643-
dc.identifier.hkuros303639-
dc.identifier.volume8-
dc.identifier.issue3-
dc.identifier.spage1942-
dc.identifier.epage1953-
dc.identifier.isiWOS:000395906900030-
dc.publisher.placeUnited Kingdom-

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