Low temperature photothermal therapy: Advances and perspectives

•The approaches to overcome the limitations in photothermal therapy have been summarized,•The role of heat shock protein to (PTT) has been discussed.•The influence of metabolic process to PTT has been described.•The challenges and future outlooks of LTPTT are also discussed. Photothermal therapy (PTT) has received increasing attention due to its high selectivity, non-invasiveness, negligible drug resistance, oxygen independence, and minimal side effects. In PTT, photothermal agents (PTAs) absorb light energy and generate heat to kill cancer cells. Although various PTAs with strong near-infrared (NIR) light absorption and high photothermal conversion efficiency have been developed, their clinical uses in PTT still face with challenges. For example, maintaining a temperature of above 50°C for several minutes is needed to effectively ablate tumors, but this high temperature may destroy the surrounding normal tissues. Moreover, this rapid heating can induce an immune response that increases the cell tolerance to heat, which can weaken the therapeutic effects of PTT. In this review, we mainly focus on two approaches that have been developed to overcome the limitations of PTT, including inhibiting the expression of heat shock protein (Hsp) and regulating the metabolic processes of cells to develop low temperature PTT (LTPTT). We then discuss the existing challenges in clinical uses of LTPTT for treating tumors, and finally introduce future perspectives on the design of more effective therapeutic agents.