装载自噬抑制剂的纳米银核介孔硅协同增强胶质瘤 放疗

Our previous studies demonstrated that silver nanoparticles (AgNPs) could be used as a potential radio-sensitizer for glioma radiotherapy enhancement, which, however, is restricted by autophagy elicitation. As one of the most promising drug-delivery carriers, mesoporous silica nanospheres (MSNs) have made great contributions to the developments of biomedicine due to their excellent drug loading performance, inherent biocompatibility, and tunable pore size. Herein, we designed autophagy inhibitor (3-me-thyladenine)-loaded AgNPs-cored MSNs, which exhibited excellent synergistic anticancer efficacy in vitro and in vivo. Besides, it was also confirmed that by inhibition of autophagy, the outcome of radiotherapy can be further enhanced. Moreover, we also explored the enhancing mechanisms from the perspective of the nuclear transcription factor Nrf2, including autophagy inhibition-related enhancement of radiation induced oxidative stress injury and the interaction of Nrf2 with autophagy. This study provided a vision of utilizing AgNPs as a potential radiosensitizer in combination with autophagy inhibitor and proposed a feasible strategy for its translation into the clinic.