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Effects of nanoparticle size on antitumor activity of 10-hydroxycamptothecin-conjugated gold nanoparticles: in vitro and in vivo studies

Authors Bao H, Zhang Q, Xu H, Yan Z

Received 15 September 2015

Accepted for publication 2 February 2016

Published 7 March 2016 Volume 2016:11 Pages 929—940

DOI https://doi.org/10.2147/IJN.S96422

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr PT Sudheesh Kumar

Peer reviewer comments 2

Editor who approved publication: Dr Lei Yang

Hanmei Bao,1,2 Qing Zhang,2,3 Hui Xu,1,2 Zhao Yan1,2

1Department of Clinical Pharmacology, 2Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, 3Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People’s Republic of China

Abstract: Gold nanoparticles (AuNPs) have emerged as a promising anticancer drug delivery scaffold. However, some controversial points still require further investigation before clinical use. A complete understanding of how animal cells interact with drug-conjugated AuNPs of well-defined sizes remains poorly understood. In this study, we prepared a series of 10-hydroxycamptothecin (HCPT)-AuNP conjugates of different sizes and compared their cytotoxic effect in vitro and antitumor effect in vivo. Transmission electron micrographs showed that the NPs had a round, regular shape with a mean diameter of ~10, 25, and 50 nm. An in vitro drug release study showed that HCPT was continuously released for 120 hours. HCPT-AuNPs showed greater cytotoxic effects on the MDA-MB-231 cell line compared with an equal dose of free HCPT. Notably, HCPT-AuNPs of an average diameter of 50 nm (HCPT-AuNPs-50) had the greatest effect. Furthermore, administration of HCPT-AuNPs-50 showed the most tumor-suppressing activity against MDA-MB-231 tumor in mice among all treatment groups. The results indicate that AuNPs not only act as a carrier but also play an active role in mediating biological effects. This work gives important insights into the design of nanoscale delivery and therapeutic systems.

Keywords: drug delivery, cancer treatment, drug-containing nanocomposites, particle size

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