Dual-enzyme catalytic nanosystem-mediated ATP depletion strategy for tumor elimination via excessive autophagy pathway

作者全名："Duan, Yifan; Wang, Jianxin; Wang, Jingjing; Yang, Qiang; Zhang, Qiuye; Lu, Shi-Yu; Zhao, Sheng; Chen, Chunmei; Sun, Yihao; Deng, Jun; Zheng, Ji; Cao, Yang; Liu, Hui"

作者地址："[Duan, Yifan; Wang, Jingjing; Yang, Qiang; Zhang, Qiuye; Zhao, Sheng; Chen, Chunmei; Sun, Yihao; Liu, Hui] Southwest Univ, Sch Mat & Energy, Key Lab Luminescence Anal & Mol Sensing, Minist Educ, Chongqing 400715, Peoples R China; [Wang, Jianxin; Cao, Yang] Chongqing Med Univ, Affiliated Hosp 2, Inst Ultrasound Imaging, Chongqing Key Lab Ultrasound Mol Imaging, Chongqing 400010, Peoples R China; [Deng, Jun] Army Med Univ, Mil Med Univ 3, Southwest Hosp, Inst Burn Res,Chongqing Key Lab Dis Proteom,State, Chongqing 400038, Peoples R China; [Wang, Jingjing] Peking Univ, Beijing Innovat Ctr Engn Sci & Adv Technol B ESAT, Sch Mat Sci & Engn, Beijing Key Lab Magnetoelectr Mat & Devices BKL MM, Beijing 100871, Peoples R China; [Lu, Shi-Yu] Chongqing Univ Sci & Technol, Coll Met & Mat Engn, Chongqing 401331, Peoples R China; [Wang, Jianxin] Harbin Med Univ, Affiliated Hosp 1, Dept Ultrasound, Harbin 150001, Peoples R China; [Zheng, Ji] Army Med Univ, Southwest Hosp, Dept Urol, Chongqing 400038, Peoples R China; [Liu, Hui] Fudan Univ, State Key Lab Mol Engn Polymers, Shanghai 201199, Peoples R China"

通信作者："Liu, H (通讯作者)，Southwest Univ, Sch Mat & Energy, Key Lab Luminescence Anal & Mol Sensing, Minist Educ, Chongqing 400715, Peoples R China.; Cao, Y (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Inst Ultrasound Imaging, Chongqing Key Lab Ultrasound Mol Imaging, Chongqing 400010, Peoples R China.; Deng, J (通讯作者)，Army Med Univ, Mil Med Univ 3, Southwest Hosp, Inst Burn Res,Chongqing Key Lab Dis Proteom,State, Chongqing 400038, Peoples R China.; Zheng, J (通讯作者)，Army Med Univ, Southwest Hosp, Dept Urol, Chongqing 400038, Peoples R China.; Liu, H (通讯作者)，Fudan Univ, State Key Lab Mol Engn Polymers, Shanghai 201199, Peoples R China."

来源：CHEMICAL ENGINEERING JOURNAL

ESI学科分类：ENGINEERING

WOS号：WOS:000801873700002

JCR分区：Q1

影响因子：15.1

年份：2022

卷号：446

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Polyaniline; Cascade catalysis; Energy depletion; Mitophagy; Excessive autophagy

摘要："Excessive autophagy is a promising pathway to eliminate tumor cells, which causes excessive damages to overload the degradation capacity of lysosomes. Designing a nanosystem that can compromise the function of lysosomes and induce severe damages simultaneously is essential to activate excessive autophagy, but is still rarely explored. Herein, a dual-enzyme catalytic nanosystem with adenosine triphosphate (ATP) depletion capacity was developed for tumor elimination via the excessive autophagy pathway. This nanosystem consisted of polyvinyl pyrrolidone-stabilized polyaniline (PANI-PVP) core, Pt nanoparticles (NPs) decoration, and glucose oxidase (GOx) payload. After being internalized by tumor cells, this formed PANI-Pt-GOx-PVP NPs could escape from the lysosome through the proton sponge effect, causing lysosomal swelling and rupturing. The Pt-GOx dualenzyme catalytic nanosystem consumes glucose to cause severe ATP shortage. This energy depletion microenvironment can not only generate intracellular damage during the GOx-mediated starvation process, but also induce mitophagy through AMPK activation. The increased accumulation of damage causes excessive autophagy, overloading the degradation capacity of lysosomes. In vivo data demonstrated that tumor growth tendency was significantly suppressed through this ATP depletion-induced excessive autophagy strategy."

基金机构："National Natural Science Foundation of China [51703184, 81630047, 92168106]; Chongqing Talents Program [CQYC201905041]; Key Project for Clinical Innovation of Army Medical University [CX2019LC107]; Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and Devices"

基金资助正文："Acknowledgments This research was funded by the National Natural Science Foundation of China (51703184, 81630047, 92168106) , Chongqing Talents Program (CQYC201905041) , and Key Project for Clinical Innovation of Army Medical University (CX2019LC107) . This research was also supported by Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and Devices."