Abstract 1327: Gold nanorods based hypoxia-targeted photothermal cancer therapy

Abstract

Abstract PURPOSE: Tumor hypoxia is a well-recognized driver of resistance to traditional cancer therapies such as chemotherapy and radiation therapy. Gold nanorods (GNR), with unique dimension and optical properties, have shown superior capability for tumor photothermal ablation. This study aimed to develop a new nanoconstruct composed of gold nanorods (GNRs) conjugate to anti-carbonic anhydrase IX (CAIX) antibody that specifically binds to CAIX, a biomarker of hypoxia, to facilitate targeting tumor hypoxic areas for focused photothermal ablation. METHODS: GNR were synthesized according to the seed-mediated growth method with modification. Transmission electron microscopy (TEM) were used to characterize the size and shape of the particles. The GNR/anti-CAIX conjugates were prepared through a bifunctional polyethylene glycol (PEG). The conjugates were characterized by UV-Vis spectra, particle sizes and zeta potentials. The binding affinity and specificity of the GNR/anti-CAIX were evaluated with ELISA, cell adhesion assay and cell photothermal treatment. HT29 colon cancer cell line (overexpressing CAIX) and NIH3T3 cell line (no expressing CAIX) were used in our study. Near-infrared (NIR) ablation was performed on HT29 tumors in mice that treated with PBS, GNR-PEG and GNR/anti-CAIX. Biodistribution were conducted on the latter two groups. RESULTS: TEM images showed that the synthesized GNR had an aspect ratio of about 3 (8 × 24 nm). The changes of UV-vis spectra, particle sizes and zeta potentials confirmed the success of the conjugation. ELISA suggested that the number of anti-CAIX per GNR was 4.8 ± 0.3. In the cell binding assay, GNR/anti-CAIX only showed specific and high degree binding to HT29 cells but not to NIH3T3 cells. NIR laser treatment of HT29 cells resulted in significantly higher killing of GNR/anti-CAIX-targeted cells than of controls. NIR ablation of HT29 tumors in mice 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. Biodistribution study showed significant higher accumulation in tumor in the targeted-GNR group. CONCLUSIONS: GNR/anti-CAIX nanoconstructs show promise as highly efficient targeting and photothermal ablation agents for cancer treatment. GRANT SUPPORT: This work was performed under funding from NIH/NIGMS grant (1SC3GM102018-01) and NIH/NIMHD/RCMI grant (5G12RR003045-21). Citation Format: Huan Xie, Sunil Krishnan. Gold nanorods based hypoxia-targeted photothermal cancer therapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1327.