TY - JOUR
T1 - Photothermal-chemotherapy with doxorubicin-loaded hollow gold nanospheres
T2 - A platform for near-infrared light-trigged drug release
AU - You, Jian
AU - Zhang, Rui
AU - Zhang, Guodong
AU - Zhong, Meng
AU - Liu, Yang
AU - Van Pelt, Carolyn S.
AU - Liang, Dong
AU - Wei, Wei
AU - Sood, Anil K.
AU - Li, Chun
N1 - Funding Information:
The authors thank Stephanie Deming for editing the manuscript and Dr. Sherry Klumpp for histologic evaluation. We also thank Mr. Kenneth Dunner for assistance with the TEM facility. This work was supported in part by National Cancer Institute grants R01 CA119387 and U54 CA151668 , the John S. Dunn Foundation, a Seed Grant through the Alliance for NanoHealth by the Department of Army Telemedicine and Advanced Technology Research Center ( W81XWH-07-2-0101 ), and the National Nature Science Foundation of China (grant 81001411 to JY). We also acknowledge the NCI Cancer Center Support Grant CA016672 , which supports MD Anderson's Small Animal Imaging Facility and TEM Core Facility.
PY - 2012/3/10
Y1 - 2012/3/10
N2 - Photothermal ablation (PTA) is an emerging technique that uses near-infrared (NIR) laser light-generated heat to destroy tumor cells. However, complete eradication of tumor cells with PTA is difficult because of uneven heat distribution in the treatment volume. We hypothesized that combining PTA with chemotherapy using a single multifunctional nanoconstruct that mediates simultaneous photothermal cell killing and drug release (photothermal- chemotherapy) would result in enhanced antitumor activity and reduced toxicity compared to chemotherapy alone. Doxorubicin (DOX) was loaded to hollow gold nanospheres (HAuNS) coated with polyethylene glycol (PEG). The pharmacokinetics and biodistribution of both DOX and HAuNS in the resulting nanoconstruct, DOX@PEG-HAuNS having different DOX:PEG:HAuNS ratios, were evaluated using dual isotope labeling techniques. The antitumor activity of DOX@PEG-HAuNS with DOX:PEG:HAuNS weight ratio of 1:3:1 (NP3) in combination with NIR laser was studied in vitro and in vivo using human MDA-MB-231 breast cancer and A2780 ovarian cancer cells. In vitro, NP3 mediated PTA of both cancer cells and DOX release upon NIR laser treatment. In vivo, NP3 showed slower clearance in blood and greater accumulation in tumors than free DOX. NP3-plus-NIR laser demonstrated greater antitumor activity than free DOX, NP3, or liposomal DOX. Moreover, NP3 displayed significantly decreased systemic toxicity compared to free DOX or liposomal DOX. Enhanced antitumor effect with NP3-plus-laser can be attributed to both the cytotoxic effect of DOX released from NP3 and the photothermal effect mediated by HAuNS. Slow release of DOX from NP3 in normal tissues contributed to reduced systemic toxicity. Photothermal-chemotherapy exemplified by a single-agent nanoconstruct NP3 is a promising approach to anticancer therapy.
AB - Photothermal ablation (PTA) is an emerging technique that uses near-infrared (NIR) laser light-generated heat to destroy tumor cells. However, complete eradication of tumor cells with PTA is difficult because of uneven heat distribution in the treatment volume. We hypothesized that combining PTA with chemotherapy using a single multifunctional nanoconstruct that mediates simultaneous photothermal cell killing and drug release (photothermal- chemotherapy) would result in enhanced antitumor activity and reduced toxicity compared to chemotherapy alone. Doxorubicin (DOX) was loaded to hollow gold nanospheres (HAuNS) coated with polyethylene glycol (PEG). The pharmacokinetics and biodistribution of both DOX and HAuNS in the resulting nanoconstruct, DOX@PEG-HAuNS having different DOX:PEG:HAuNS ratios, were evaluated using dual isotope labeling techniques. The antitumor activity of DOX@PEG-HAuNS with DOX:PEG:HAuNS weight ratio of 1:3:1 (NP3) in combination with NIR laser was studied in vitro and in vivo using human MDA-MB-231 breast cancer and A2780 ovarian cancer cells. In vitro, NP3 mediated PTA of both cancer cells and DOX release upon NIR laser treatment. In vivo, NP3 showed slower clearance in blood and greater accumulation in tumors than free DOX. NP3-plus-NIR laser demonstrated greater antitumor activity than free DOX, NP3, or liposomal DOX. Moreover, NP3 displayed significantly decreased systemic toxicity compared to free DOX or liposomal DOX. Enhanced antitumor effect with NP3-plus-laser can be attributed to both the cytotoxic effect of DOX released from NP3 and the photothermal effect mediated by HAuNS. Slow release of DOX from NP3 in normal tissues contributed to reduced systemic toxicity. Photothermal-chemotherapy exemplified by a single-agent nanoconstruct NP3 is a promising approach to anticancer therapy.
KW - Doxorubicin
KW - Near-infrared light
KW - Pharmacokinetics
KW - Photothermal ablation therapy
KW - Triggered release
UR - http://www.scopus.com/inward/record.url?scp=84858700151&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84858700151&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2011.10.028
DO - 10.1016/j.jconrel.2011.10.028
M3 - Article
C2 - 22063003
AN - SCOPUS:84858700151
SN - 0168-3659
VL - 158
SP - 319
EP - 328
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 2
ER -