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Photothermal therapy (PTT) has been widely investigated as a regimen for superficial tumors. However, conventional PTT strategies usually require photothermal temperatures above 50 °C to achieve significant therapeutic efficacy, which in effect would lead to injury to adjacent normal tissues and meanwhile, the heat generated by the photothermal effect would induce inflammation owing to the damage to cytoplasmic components. In order to reduce the toxicity of photothermal therapy and increase the efficiency of photothermal tumor destruction, novel strategies are prerequisite for targeted regimen and surveillance of photothermal therapy in real time. In this paper, we reported a concave mesoporous polydopamine-targeting nanotherapeutic agent. We employed B-MPDA as the carrier and encapsulated CQ and ASP to yield B-MPDA/CQ/ASP which was loaded with autophagy inhibitors and anti-inflammatory agents and coated uniformly with MnO2 Nanosheet. With HA functionalizing MnO2 Nanosheet, B-MPDA/CQ/ASP@MnO2-HA was constituted. The yielded nanoparticles were identified to be advantageous for good biocompatibility, potent targeting and low toxicity. In anti-tumor regimens, the nanoparticles can be applied to hyaluronic acid targeting, mesoporous polydopamine thermotherapy, and autophagy inhibitor sensitization thermotherapy, and simultaneously eliminate the inflammatory effects induced by photothermal therapy. Furthermore, in combination with the anti-inflammatory effect of targeting tumor, this agent can effectively induce apoptosis of cancer cells and significantly improve the efficiency of mild photothermal killing of cancer cells, which provides insight into the development of nanoparticles and application to mild photothermal therapy in the clinical scenario.