The tumor microenvironment is complex and changeable, so the design of nano-delivery system for tumor microenvironment has attracted wide attention. Based on this, we designed an intelligent nano-reactor for the characteristics of acidic pH and hypoxia in tumor microenvironment. Firstly, the silver nanocubes was synthesized by the biological template method, which exhibited a good photothermal conversion efficiency and can realize the photothermal treatment of tumor sites. Subsequently, the hypoxic prodrug TPZ and polydopamine for chemotherapy were self-assembled. After polydopamine arrived at the tumor site (pH 5.5) from the normal physiological environment (pH 7.4), the hypoxic prodrug TPZ was released in pH response by polydopamine. Subsequently, TPZ selectively induced obvious cell damage under tumor hypoxia stimulation, but had no toxic effect on normal cells under normal oxygen. In addition, the nano-converter was loaded with tumor cell membrane on the surface, which enhanced the targeted delivery of the nano-reactor to achieve a highly effective anti-tumor effect. The nano-reactor was capable of combining photothermal/ chemotherapy therapy. Importantly, it can selectively kill tumor cells without damaging normal cells based on the characteristics of the tumor microenvironment, with high bio-safety and clinical transformation potential.

Fig 1: Graphical abstract of highly active nanoreactors for regulating tumor microenvironment and antitumor therapy.