Hypoxia-targeted gold nanorods for cancer photothermal therapy

// Yuan Chen 1 , Xiaomei Bian 1 , Maureen Aliru 2 , Amit A. Deorukhkar 2 , Oscar Ekpenyong 1 , Su Liang 1 , Jyothy John 1 , Jing Ma 1 , Xiuqing Gao 1 , Jon Schwartz 3 , Pankaj Singh 2 , Yuanqing Ye 4 , Sunil Krishnan 2 and Huan Xie 1 1 Department of Pharmaceutical and Environmental Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, USA 2 Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA 3 Nanospectra Biosciences, Inc., Houston, Texas, USA 4 Department of Epidemiology, Division of OVP, Cancer Prevention and Population Science, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA Correspondence to: Sunil Krishnan, email: SKrishnan@mdanderson.org Huan Xie, email: huan.xie@tsu.edu Keywords: gold nanorods; hypoxia; carbonic anhydrase IX; photothermal therapy; hyperspectral imaging Received: February 20, 2018     Accepted: May 08, 2018     Published: May 29, 2018 ABSTRACT 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.