Abstract 3903: Optimizing the antitumor efficacy of AuNR-assisted plasmonic photothermal therapy and its molecular impact
Authors: Rahman Mohammad Aminur , Ali Moustafa R. K. , Zhao Zhixiang , Chen Georgia Z. , El-Sayed Mostafa A. , Shin Dong M. 
Published: July 2016

Plasmonic gold nanorods (AuNRs) are very promising for biomedical applications because of their strongly enhanced radiation (e.g. absorption and scattering) and non-radioactive photothermal properties due to surface plasmon resonance. In plasmonic photothermal therapy (PPTT), AuNRs absorb near infrared (NIR) laser and induce localized heat (i.e., hyperthermia) which can promote tumor tissue ablation. However, the lack of comprehensive studies to improve the efficiency of AuNRs has hindered their application. The objectives of this study were to perform a systematic analysis to optimize AuNR-PPTT based on different sizes, formulation and concentration along with various laser powers for cancer therapy in vitro and in vivo. We used AuNRs of sizes 26×6 nm and 72×19 nm with concentrations of 2.5, 5 and 10 nM, followed by 2 min of 0.5, 1, 1.78 W/cm2 NIR 808 nm diode laser exposure both in vitro and in vivo. For in vitro studies, we studied several head and neck squamous cell carcinoma (HNSCC) cell lines. We conducted an in vivo antitumor efficacy study in nude mice bearing human HNSCC Tu686 xenograft tumors with three formulations of AuNRs (72×19 nm and 26×6 nm with or without rifampicin (Rf) conjugation).Single dose intratumoral injection of 5 nM and 10 nM AuNRs (26×6 nm), followed by 2 min of 1.78 W/cm2 NIR laser exposure inhibited tumor growth and the 2.5 nM dose led to moderate antitumor efficacy. However, we observed severe skin burning at higher concentrations. In contrast, AuNRs (72×19nm) had no remarkable antitumor efficacy at high laser power. Impressively, small AuNR-conjugated Rf (AuNR-Rf) accumulated AuNRs inside the cell and had very significant antitumor efficacy (p&lt;0.05) without any skin burning at 2.5 nM concentration. We confirmed our observations by immunohistochemistry staining of proliferation marker Ki67 in tumor tissues. To understand the molecular impact, we applied the optimized treatment in vitro. AuNR-Rf was able to induce apoptosis in 24 hours of treatment and decreased cell viability, as supported by immunoblotting of PARP and caspase 3 cleavage. In addition, we found that mutant p53 was completely abolished in AuNR-PPTT treatment. Overall, we have demonstrated that 2.5 nM AuNR with 1.78 W/cm2 NIR laser has no remarkable toxicities and optimal antitumor efficacy was observed by conjugation with Rf. In future studies, we will explore potential novel biomarkers by next generation sequencing (NGS) in mouse tumor tissues to determine the response to AuNR-PPTT. (This study supported by U01CA151802).

[M.A.R. and M.R.K.A. contributed equally to this work.]

Citation Format: Mohammad Aminur Rahman, Moustafa R. K. Ali, Zhixiang Zhao, Georgia Z. Chen, Mostafa A. El-Sayed, Dong M. Shin. Optimizing the antitumor efficacy of AuNR-assisted plasmonic photothermal therapy and its molecular impact. [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 3903.