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

扫码查看

原文链接

NETL
NSTL
万方数据

外文摘要：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 photother-apy.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.

外文关键词：

AutophagyTumor phototherapySynergistic sensitizationHCQTRANSFERRINDisulfide bond reconstructionGSHBiomimetic mineralized nano-tellurium

作者：

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

展开 >

作者单位：

School of Pharmaceutical Sciences,Zhengzhou University,Zhengzhou 450001,China

Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases,Zhengzhou 450001,China

Collaborative Innovation Center of New Drug Research and Safety Evaluation,Zhengzhou 450001,China

School of Chemistry and Molecular Engineering,Zhengzhou University,Zhengzhou 450001,China

展开 >

基金：

国家自然科学基金国家自然科学基金国家自然科学基金Key Program for Science and Technology Research in Henan Province,ChinaTraining Plan for Young Backbone Teachers in Higher Education Institutions of Henan Province,China

项目编号：

8210291881972893821727192321023110932021ZDGGJS054

出版年：

2024

DOI：

10.1016/j.apsb.2023.11.019

药学学报(英文版)

CSTPCD

ISSN：

年,卷(期)：2024.14(5)

参考文献量1