Magnifying the therapeutic effect of photodynamic therapy via heat shock protein inhibition

A combined strategy using various heat shock protein (HSP) inhibitors as potentiators to magnify the therapeutic effect of cancer photodynamic therapy (PDT) is proposed. The results indicate that both HSP70 and HSP90 inhibitors are beneficial to enhance the cytotoxicity of photosensitizers. Notably, HSP90 inhibitors can reduce the intracellular expression of ATR protein and block the reactive oxygen species (ROS)-induced DNA damage repair pathway in cells caused by type I PDT; for type II PDT, the inhibitors can inhibit the function of P-glycoprotein efflux pumps, thereby promoting the intracellular accumulation of photosensitizers. These combined effects not only reverse the stress defense mechanism in tumor cells, but also markedly boost the cytotoxicity of PDT.