Hyaluronic acid-covered piezoelectric nanocomposites as tumor microenvironment modulators for piezoelectric catalytic therapy of melanoma

Increasing the formation of reactive oxygen species (ROS) and reducing the elimination of ROS are the two main objectives in the development of novel inorganic sonosensitizers for use in sonodynamic therapy (SDT). Therefore, BTO-Pd-MnO2-HA nanocomplexes with targeted tumor cells and degradable oxygen-producing shells were designed as piezoelectric sonosensitizers for enhancing SDT. The deposition of palladium particles (Pd NPs) leads to the formation of Schottky junctions, promoting the separation of electron-hole pairs and thereby increasing the efficiency of toxic ROS generation in SDT. The tumor microenvironment (TME) triggers the degradation of MnO2, and the released Mn2+ ions catalyze the generation of hydroxyl radicals (center dot OH) from H2O2 through a Fenton-like reaction. BTO-Pd-MnO2-HA can continuously consume glutathione (GSH) and generate O2, thereby improving the efficiency of SDT and chemodynamic therapy (CDT). A multistep enhanced SDT process mediated by the piezoelectric sonosensitizers BTO-Pd-MnO2-HA was designed, targeted by hyaluronic acid (HA), activated by decomposition in TME, and amplified by deposition of Pd. This procedure not only presents a new alternative for the improvement of sonosensitizers but also widens the application of piezoelectric nanomaterials in biomedicine.

Automated summary

To enhance sonodynamic therapy (SDT), a BTO-Pd-MnO2-HA nanocomplex with targeted tumor cells and degradable oxygen-producing shells was designed as a piezoelectric sonosensitizer. Palladium particles (Pd NPs) were deposited to form Schottky junctions, increasing the efficiency of toxic reactive oxygen species (ROS) generation. The degradation of MnO2 in the tumor microenvironment (TME) triggered the production of hydroxyl radicals (center dot OH) through a Fenton-like reaction. By continuously consuming glutathione (GSH) and generating O2, BTO-Pd-MnO2-HA improved the efficiency of SDT and chemodynamic therapy (CDT).