Nanomedicine-Enabled Mild Photothermal Therapy Strategies for Enhanced Antitumor Treatment

Photothermal therapy (PTT) has emerged as a promising approach for tumor ablation utilizing hyperthermia offers several advantages, including non-invasiveness, spatiotemporal controllability, and notable therapeutic efficacy. However, the clinical application of PTT is challenged by the heat diffusion. To address this, mild PTT (mPTT) has gained attention as an alternative strategy, operating at temperatures below 45 °C, with remarkable antitumor effects and minimal thermal damage to nearby normal tissues. Despite these benefits, the expression of heat shock proteins (HSPs) induces thermal resistance, which limits the therapeutic potential and practical implementation of mPTT. Nanomedicines have emerged as a solution to overcome these challenges, offering improved solubility, prolonged circulation time, enhanced tumor accumulation, and controlled cargo release, surpassing the capabilities of small molecular HSP inhibitors. Herein, it has been aimed to discuss the current landscape of photothermal agents, elucidate the underlying mechanisms of mPTT, highlight the benefits of mPTT in combination therapy, and explore the potential of nanomedicines to enhance mPTT efficacy. Additionally, future directions for the development of mPTT are presented and the challenges that are needed to be addressed are identified, with the aim of encouraging further research contributions to advance mPTT toward clinical applications.