The Study Of The Application Of Gold Nanomaterials In Enhanced Tumor Photothermal Therapy By Regulation Of Autophagy

Tumor has become one of the major diseases that seriously threaten human health.The combination of radiotherapy and chemotherapy,which shows a synergistic effect on tumor therapy,is a common treatment in clinic practice.However,the development of new strategies to improve chemo/radiotherapy is of great importance due to the resistance developed by radiotherapy and the non-specific damage to the tumor tissue microenvironment by ionizing radiation and chemotherapeutic drugs.Nanomaterialmediated photothermal therapy(PTT)can ameliorate these side effects,but it also brings new problems and challenges,such as unevenly distributed high temperature,which leads to incomplete tumor eradication and severe damage to healthy tissue.Previous studies have confirmed that autophagy can be activated in tumor cells by PTT,and inhibiting cellular autophagy process can significantly enhance the efficacy of photothermal effect of killing tumor cells.Based on this,a novel gold nanomaterial drug delivery system CDBAuNCs was synthesized,and its synergistic enhancement effect of PTT on tumor were systematically studied.CDBAuNCs consists of gold nanocages(AuNCs)loaded with doxorubicin(DOX)and autophagy inhibitor Bafilomycin A1(BAF)as the core of the nanoparticles,the cell membrane(CMV)that extracted from breast cancer cells(4T1)in vitro served as outer shell of AuNCs.CDBAuNCs has three characteristics: specific targeting of 4T1 cells,autophagy inhibition,and PTT.In vitro and in vivo experimental studies displayed that targeting of 4T1 cells by CMV increases the cellular uptake rate of CDBAuNCs.Under near-infrared(NIR)irradiation,the hyperthermia generated by AuNCs can destroy the CMV shell on CDBAuNCs,which enables CDBAuNCs to release the loaded drugs DOX and BAF at lower temperature.On the one hand,the released DOX promote tumor cell apoptosis;On the other hand,BAF can synergistically enhance PTT of tumor cells by inhibiting cellular autophagy.Finally,CDBAuNCs can play a role in effectively killing tumor cells and inhibiting tumor growth under mild conditions.The synthesis and the effect in PTT of CDBAuNCs are expected to provide new ideas and theoretical basis for clinical treatment of breast cancer.