A facile composite nanoparticle promoted by photoelectron transfer and consumption for tumor combination therapy

Abstract

Titanium dioxide nanoparticles are a promising agent for oxygen-independent Type I photodynamic therapy (PDT). However, the low separation efficiency of electron–hole pairs limits their application. It is reported that Cu₂(OH)PO₄ can enhance the electron–hole pair separation of semiconductors, and its OCT Cu^II crystal form can be reduced to Cu^I under certain conditions. However, whether photo-generated electrons can reduce Cu^II in Cu₂(OH)PO₄ is unknown. Therefore, based on a simple hydrothermal method, a Cu₂(OH)PO₄ layer is composited on the surface of NIR-induced photothermal blue titanium dioxide nanoparticles (BT NPs) to form BT@Cu₂(OH)PO₄ composite nanoparticles (BTCu NPs). Through detection of the ˙OH and Cu^I generation, it can be found that the Cu₂(OH)PO₄ layer can not only promote the separation of electron–hole pairs through electron transfer to enhance PDT, but also can generate Cu^I to realize a Fenton-like reaction with H₂O₂ to achieve CDT. Compared with the BT NPs, the electron–hole separation efficiency of BTCu NPs is improved by 35.3%, and the ˙OH generation capacity is increased by 56% under the condition of adding H₂O₂. In HepG2 cells, the ROS generation ability of BTCu NPs is increased by 60%, and the apoptosis rate and necrosis rate are increased by 46% and 53%, respectively. That is, by one NIR laser, the combination of photo-thermal/photo-dynamic/chemo-dynamic therapy (PTT/PDT/CDT) is realized. Besides, the BTCu NPs caused significant lysosomal membrane permeabilization (LMP) and mitochondrial membrane potential depolarization, indicating a lysosomal–mitochondrial death pathway.