Positron Emission Tomography-Assisted Photothermal Therapy with Gold Nanorods

Photothermal anticancer therapy based on plasmonic nanoparticles is proposed to enhance treatment efficacy while mitigating unintended side effects. However, most studies blindly rely on the accumulation of nanoparticles at the tumor site, which may result in inefficient treatment. In this study, the aim is to evaluate relevant parameters to improve plasmonic photothermal therapy. Gold nanorods (AuNRs) with an optimized aspect ratio and either amino or carboxylic acid surface functionalization are selected as photothermal agents. AuNR biocompatibility and photothermal activity in 2D and 3D human MDA-MB-231 triple-negative breast cancer cell models, evaluating localized hyperthermal cell death upon irradiation with resonant near-infrared (NIR) light, are analyzed first. To ensure reliable tracking of biodistribution in vivo, AuNRs are labeled with the positron emitter copper-64 (64Cu), and their distribution in a murine MDA-MB-231 tumor model is studied via positron emission tomography (PET) imaging. PET images reveal enhanced tumor accumulation of carboxylic acid-functionalized AuNRs compared to amino-functionalized AuNRs post-intravenous administration. Relatively low NIR laser power densities (0.5 W cm-2) are used for controlled heating - keeping local temperature below 50 degrees C - upon irradiation of intravenously and intratumorally administered AuNRs. As a result, tumor growth is significantly decelerated, even 9 days after application of photothermal therapy. This study explores nanoparticle-assisted photothermal therapy by assessing gold nanorods (AuNRs) of various aspect ratios and surface functionalization as photothermal agents. In vivo positron emission tomography imaging highlights enhanced tumor accumulation of carboxylic acid-functionalized AuNRs, sufficient for effective hyperthermal cell death in a mouse breast cancer model. image