Enhanced efficacy of photothermal therapy by combining a semiconducting polymer with an inhibitor of a heat shock protein

Photothermal therapy (PTT) is a highly effective therapeutic modality in tumor therapy. Nevertheless, the PTT of cancer is also accompanied by thermoresistance of cells, which may alleviate the PTT efficacy or even lead to tumor recurrence. Heat shock protein 90 (HSP90) is closely related to the resistance, so a combination of inhibitors of HSP90 and photothermal agents could improve the PTT efficacy. In this work, gambogic acid (GA), an inhibitor of HSP90, is incorporated into a photothermal nanoagent, so as to reduce the influence of thermoresistance and maximize the PTT efficiency. Poly((2,5-diyl-2,3,5,6-tetrahydro-3,6-dioxo-pyrrolo(3,4-c)pyrrole-1,4-diyl)-alt-(2,2:5,2-terthiophene-5,5-diyl)) (PDPP3T) is selected as the robust photothermal material, and polymer-GA nanoparticles (PGNPs) incorporating both GA and PDPP3T are prepared. The PGNPs exhibit excellent photothermal activity with a high photothermal conversion efficiency of 36%, and great heating reproducibility and photoacoustic imaging performance. Besides, PGNPs are stable enough in water, in physiological conditions or under irradiation. The inhibition of HSP90 dramatically increases the apoptosis rate of cells, accordingly promoting the efficacy of PTT. Mice treated with PGNPs under 808 nm laser irradiation possess the most effective tumor inhibition, while no obvious systemic toxicity has been observed. Our study provides a valid approach to improve the PTT efficacy for more potent cancer therapy.