Reductive damage induced autophagy inhibition for tumor therapy - Details

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Abstract：

Numerous　therapeutic　anti-tumor　strategies　have　been　developed　in　recent　decades.　However,　their　therapeutic　efficacy　is　reduced　by　the　intrinsic　protective　autophagy　of　tumors.　Autophagy　plays　a　key　role　in　tumorigenesis　and　tumor　treatment,　in　which　the　overproduction　of　reactive　oxygen　species　(ROS)　is　recognized　as　the　direct　cause　of　protective　autophagy.　Only　a　few　molecules　have　been　employed　as　autophagy　inhibitors　in　tumor　therapy　to　reduce　protective　autophagy.　Among　them,　hydroxychloroquine　is　the　most　commonly　used　autophagy　inhibitor　in　clinics,　but　it　is　severely　limited　by　its　high　therapeutic　dose,　significant　toxicity,　poor　reversal　efficacy,　and　nonspecific　action.　Herein,　we　demonstrate　a　reductive-damage　strategy　to　enable　tumor　therapy　by　the　inhibition　of　protective　autophagy　via　the　catalytic　scavenging　of　ROS　using　porous　nanorods　of　ceria　(PN-CeO2)　nanozymes　as　autophagy　inhibitor.　The　antineoplastic　effects　of　PN-CeO2　were　mediated　by　its　high　reductive　activity　for　intratumoral　ROS　degradation,　thereby　inhibiting　protective　autophagy　and　activating　apoptosis　by　suppressing　the　activities　of　phosphatidylinositide　3-kinase/protein　kinase　B　and　p38　mitogen-activated　protein　kinase　pathways　in　human　cutaneous　squamous　cell　carcinoma.　Further　investigation　highlighted　PN-CeO2　as　a　safe　and　efficient　anti-tumor　autophagy　inhibitor.　Overall,　this　study　presents　a　reductive-damage　strategy　as　a　promising　anti-tumor　approach　that　catalytically　inhibits　autophagy　and　activates　the　intrinsic　antioxidant　pathways　of　tumor　cells　and　also　shows　its　potential　for　the　therapy　of　other　autophagy-related　diseases.　[Figure　not　available:　see　fulltext.]　©　2022,　Tsinghua　University　Press.

Keyword：

autophagy inhibitor; CeO2; reactive oxygen species; reductive damage; tumor therapy

Author Community：

[ 1 ] [Wang Y.]Department of Dermatology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, China
[ 2 ] [Wang Y.]Key Laboratory of Special Functional and Smart Polymer Materials of Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi’an, 710072, China
[ 3 ] [Wang Y.]Department of Dermatology, the Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, 710004, China
[ 4 ] [Huang Y.]Department of Dermatology, the Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, 710004, China
[ 5 ] [Fu Y.]School of Chemical Engineering and Technology, Shaanxi Key Laboratory of Energy Chemical Process Intensification, Xi’an Jiaotong University, Xi’an, 710049, China
[ 6 ] [Guo Z.]Key Laboratory of Special Functional and Smart Polymer Materials of Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi’an, 710072, China
[ 7 ] [Chen D.]Key Laboratory of Special Functional and Smart Polymer Materials of Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi’an, 710072, China
[ 8 ] [Cao F.]Key Laboratory of Special Functional and Smart Polymer Materials of Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi’an, 710072, China
[ 9 ] [Ye Q.]Department of Urology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, China
[ 10 ] [Duan Q.]Department of Dermatology, the Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, 710004, China
[ 11 ] [Liu M.]Department of Dermatology, the Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, 710004, China
[ 12 ] [Wang N.]Department of Dermatology, the Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, 710004, China
[ 13 ] [Han D.]Department of Dermatology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, China
[ 14 ] [Qu C.]Xi’an People’s Hospital (Xi’an Fourth Hospital), Shaanxi Eye Hospital, Affiliated Guangren Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, 710004, China
[ 15 ] [Tian Z.]Key Laboratory of Special Functional and Smart Polymer Materials of Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi’an, 710072, China
[ 16 ] [Qu Y.]Key Laboratory of Special Functional and Smart Polymer Materials of Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi’an, 710072, China
[ 17 ] [Zheng Y.]Department of Dermatology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, China

Reprint Author's Address：

Y. Zheng;;Department of Dermatology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, China;;email: zhengyan2018@xjtu.edu.cn;;Z. Tian;;Key Laboratory of Special Functional and Smart Polymer Materials of Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi’an, 710072, China;;email: zhimintian@nwpu.edu.cn;;Y. Qu;;Key Laboratory of Special Functional and Smart Polymer Materials of Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi’an, 710072, China;;email: yongquan@nwpu.edu.cn;;

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Source ：

Nano Research

ISSN： 1998-0124

Year： 2022

8 . 8 9 7

JCR@2020

ESI Discipline： PHYSICS;

ESI HC Threshold：6

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