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

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

Acknowledgments

We thank Prof Ruifang Niu (Tianjin Medical University Cancer Institute and Hospital) for the gift of the MDA-MB-231-luc cells. This work was supported by National Science and Technology Major Project (No. 2013ZX09303001) and Tianjin Medical University Cancer Institute and Hospital fund (No. B1205).

Author contributions

Zhao Yan and Hanmei Bao designed the research. Hanmei Bao, Qing Zhang, and Hui Xu undertook the research. Hanmei Bao and Qing Zhang analyzed the data. Zhao Yan and Hanmei Bao wrote the paper. All authors contributed toward data analysis, drafting and critically revising the paper and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.