In situ autophagy regulation in synergy with phototherapy for breast cancer treatment  

作　　者：Huijuan Zhang Xiangyang Xuan Yaping Wang Zijun Qi Kexuan Cao Yingmei Tian Chaoqun Wang Junbiao Chang Zhenzhong Zhang Lin Hou 

机构地区：[1]School of Pharmaceutical Sciences,Zhengzhou University,Zhengzhou 450001,China [2]Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases,Zhengzhou 450001,China [3]Collaborative Innovation Center of New Drug Research and Safety Evaluation,Zhengzhou 450001,China [4]School of Chemistry and Molecular Engineering,Zhengzhou University,Zhengzhou 450001,China

出　　处：《Acta Pharmaceutica Sinica B》2024年第5期2317-2332,共16页药学学报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(Nos.82102918,81972893 and 82172719);the Key Program for Science and Technology Research in Henan Province(No.232102311093,China);the Training Plan for Young Backbone Teachers in Higher Education Institutions of Henan Province(No.2021ZDGGJS054,China).

摘　　要：Autophagy is an important factor in reducing the efficacy of tumor phototherapy(including PTT and PDT).Accurate regulation of autophagy in tumor cells is a new strategy to improve the anti-tumor efficiency of PTT/PDT.This project intended to construct a tumor-activated autophagy regulator to efficiently block PTT/PDT-induced autophagy and realize synergistic sensitization to tumor phototherapy.To achieve this goal,we first synthesized TRANSFERRIN(Tf)biomimetic mineralized nano-tellurium(Tf-Te)as photosensitizer and then used disulfide bond reconstruction technology to induce Tf-Te self-assembly.The autophagy inhibitor hydroxychloroquine(HCQ)and iron ions carried by Tf were simultaneously loaded to prepare a tumor-responsive drug reservoir Tf-Te/HCQ.After entering breast cancer cells through the“self-guidance system”,Tf-Te/HCQ can generate hyperpyrexia and ROS under NIR laser irradiation,to efficiently induce PTT/PDT effect.Meanwhile,the disulfide bond broke down in response to GSH,and the nanoparticles disintegrated to release Fe2+and HCQ at fixed points.They simultaneously induce lysosomal alkalinization and increased osmotic pressure,effectively inhibit autophagy,and synergistically enhance the therapeutic effect of phototherapy.In vivo anti-tumor results have proved that the tumor inhibition rate of Tf-Te/HCQ can be as high as 88.6%on 4T1 tumor-bearing mice.This multifunctional drug delivery system might provide a new alternative for more precise and effective tumor phototherapy.

关 键 词：AUTOPHAGY Tumor phototherapy Synergistic sensitization HCQ TRANSFERRIN Disulfide bond reconstruction GSH Biomimetic mineralized nano-tellurium 

分 类 号：R575[医药卫生—消化系统]