装载自噬抑制剂的纳米银核介孔硅协同增强胶质瘤放疗

Autophagy inhibitor-loaded mesoporous AgNPs@SiO2 nanoplatform for synergistically enhanced glioma radiotherapy

先前研究表明,银纳米颗粒可作为潜在的胶质瘤放疗的增敏剂,但这一作用受到自噬的限制.作为最有前途的药物递送载体之一,介孔二氧化硅纳米球由于其优异的药物负载性能、固有的生物相容性和可调节的孔径,对生物医学的发展做出了巨大贡献.在此,我们设计了一种负载自噬抑制剂3-甲基腺嘌呤的纳米银核介孔二氧化硅纳米球,其在体外和体内均表现出优异的协同抗癌作用.并且证实了抑制自噬可以进一步改善胶质瘤放疗的效果.此外,还从与氧化应激相关的核转录因子Nrf2的角度探讨了可能的机制,包括自噬抑制增强辐射诱导的氧化应激损伤以及Nrf2与自噬的相互作用.这项研究为将纳米银作为与自噬抑制剂结合用于胶质瘤放射增敏提供了一个愿景,并为其临床转化提供了一种可行的策略.

Our previous studies demonstrated that silver nanoparticles(AgNPs)could be used as a potential radiosensitizer 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-methyladenine)-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.