International Journal of Nanomedicine (Dec 2018)
Gold nanorod-encapsulated biodegradable polymeric matrix for combined photothermal and chemo-cancer therapy
Abstract
Chun-Chiao Chuang,1,* Chih-Chi Cheng,1,* Pei-Ying Chen,1 Chieh Lo,1 Yi-Ning Chen,1 Min-Hsiung Shih,2,3 Chien-Wen Chang1 1Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan, Republic of China; 2Research Center of Applied Sciences (RCAS), Academia Sinica, Taipei, 11529, Taiwan, Republic of China; 3Department of Photonics, National Chiao Tung University (NCTU), Hsinchu, 30010, Taiwan, Republic of China *These authors contributed equally to this work Purpose: A biocompatible nanocomplex system co-encapsulated with gold nanorods (AuNRs) and doxorubicin (DOX) was investigated for its potentials on the combined photothermal- and chemotherapy.Materials and methods: Hydrophobic AuNRs were synthesized by the hexadecyltrimethylammonium bromide (CTAB)-mediated seed growth method, and then, they received two-step surface modifications of polyethylene glycol (PEG) and dodecane. The AuNR/DOX/poly(lactic-co-glycolic acid) (PLGA) nanocomplexes were prepared by emulsifying DOX, AuNR, and PLGA into aqueous polyvinyl alcohol solution by sonication. Human serum albumin (HSA) was used to coat the nanocomplexes to afford HSA/AuNR/DOX–PLGA (HADP). Size and surface potential of the HADP nanocomplexes were determined by using a Zetasizer. Cytotoxicity and cellular uptake of the HADP were analyzed by using MTT assay and flow cytometry, respectively. In vitro anticancer effects of the HADP were studied on various cancer cell lines. To assess the therapeutic efficacy, CT26 tumor-bearing mice were intravenously administered with HADP nanocomplexes and laser treatments, followed by monitoring of the tumor growth and body weight.Results: Size and surface potential of the HADP nanocomplexes were 245.8 nm and -8.6 mV, respectively. Strong photothermal effects were verified on the AuNR-loaded PLGA nanoparticles (NPs) in vitro. Rapid and repeated drug release from the HADP nanocomplexes was successfully achieved by near-infrared (NIR) irradiations. HSA significantly promoted cellular uptake of the HADP nanocomplexes to murine colon cancer cells as demonstrated by cell imaging and flow cytometric studies. By combining photothermal and chemotherapy, the HADP nanocomplexes exhibited strong synergistic anticancer effects in vitro and in vivo.Conclusion: An NIR-triggered drug release system by encapsulating hydrophobic AuNR and DOX inside the PLGA NPs has been successfully prepared in this study. The HADP NPs show promising combined photothermal- and chemotherapeutic effects without inducing undesired side effects on a murine colon cancer animal model. Keywords: gold nanomaterials, photothermal therapy, triggered drug release, albumin, biodegradable nanoparticles
