Despite its success against cancer, photothermal therapy (PTT) (>50 °C) suffers from several limitations such as triggering inflammation and facilitating immune escape and metastasis and also damage to the surrounding normal cells. Mild-temperature PTT has been proposed to override these shortcomings. We developed a nanosystem using HepG2 cancer cell membrane-cloaked zinc glutamate-modified Prussian blue nanoparticles with triphenylphosphine-conjugated lonidamine (HmPGTL NPs). This innovative approach achieved an efficient mild-temperature PTT effect by downregulating the production of intracellular ATP. This disrupts a section of heat shock proteins that cushion cancer cells against heat. The physicochemical properties, anti-tumor efficacy, and mechanisms of HmPGTL NPs both in vitro and in vivo were investigated. Moreover, the nanoparticles cloaked with the HepG2 cell membrane substantially prolonged the circulation time in vivo. Overall, the designed nanocomposites enhance the efficacy of mild-temperature PTT by disrupting the production of ATP in cancer cells. Thus, we anticipate that the mild-temperature PTT nanosystem will certainly present its enormous potential in various biomedical applications.
Keywords: Prussian blue nanoparticles; cancer cell membrane; heat shock proteins; lonidamine; mild-temperature photothermal therapy.