Hypoxia-targeted gold nanorods for cancer photothermal therapy
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Yuan Chen1, Xiaomei Bian1, Maureen Aliru2, Amit A. Deorukhkar2, Oscar Ekpenyong1, Su Liang1, Jyothy John1, Jing Ma1, Xiuqing Gao1, Jon Schwartz3, Pankaj Singh2, Yuanqing Ye4, Sunil Krishnan2 and Huan Xie1
1Department of Pharmaceutical and Environmental Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, USA
2Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA
3Nanospectra Biosciences, Inc., Houston, Texas, USA
4Department of Epidemiology, Division of OVP, Cancer Prevention and Population Science, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA
Sunil Krishnan, email: [email protected]
Huan Xie, email: [email protected]
Keywords: gold nanorods; hypoxia; carbonic anhydrase IX; photothermal therapy; hyperspectral imaging
Received: February 20, 2018 Accepted: May 08, 2018 Published: May 29, 2018
Tumor hypoxia is a well-recognized driver of resistance to traditional cancer therapies such as chemotherapy and radiation therapy. We describe development of a new nanoconstruct composed of gold nanorods (GNRs) conjugated to carbonic anhydrase IX (CAIX) antibody that specifically binds to CAIX, a biomarker of hypoxia, to facilitate targeting tumor hypoxic areas for focused photothermal ablation. Physicochemical characterization studies confirmed the size, shape, monodispersity, surface charge, and serum stability of the GNRs. Enzyme-linked immunosorbent assays and cellular binding and uptake studies confirmed successful conjugation of antibody to the GNRs and specificity for CAIX. Near-infrared irradiation of CAIX-overexpressing cells treated with GNR/anti-CAIX resulted in significantly higher cell death than cells treated with control GNRs. In vivo biodistribution studies using hyperspectral imaging and inductively coupled plasma mass spectrometry confirmed intravenous administration results not only in greater accumulation of GNR/anti-CAIX in tumors than control GNRs but also greater penetration into hypoxic areas of tumors. Near-infrared ablation of these tumors showed no tumor regression in the sham-treated group, regression but recurrence in the non-targeted-GNR group, and complete tumor regression in the targeted-GNR group. GNR/anti-CAIX nanoconstructs show promise as hypoxia targeting and photothermal ablation agents for cancer treatment.
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