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

Zhang, YH (Zhang, Yahui)^{[ 1 ]} ; Sha, WZ (Sha, Weizhou)^{[ 1 ]} ; Liu, Y (Liu, Yang)^{[ 1 ]} ; Wang, W (Wang, Wei)^{[ 1 ]} ; Yuan, Z (Yuan, Zhi)^{[ 1,2 ]}

MATERIALS CHEMISTRY FRONTIERS, 2020, 4(10): 3047-3056

DOI: 10.1039/d0qm00447b

摘要

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 Cu-2(OH)PO(4)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 Cu-2(OH)PO(4)is unknown. Therefore, based on a simple hydrothermal method, a Cu-2(OH)PO(4)layer is composited on the surface of NIR-induced photothermal blue titanium dioxide nanoparticles (BT NPs) to form BT@Cu-2(OH)PO(4)composite nanoparticles (BTCu NPs). Through detection of the degrees OH and Cu(I)generation, it can be found that the Cu-2(OH)PO(4)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 H(2)O(2)to achieve CDT. Compared with the BT NPs, the electron-hole separation efficiency of BTCu NPs is improved by 35.3%, and the degrees 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.