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      Artesunate-loaded poly (lactic-co-glycolic acid)/polydopamine-manganese oxides nanoparticles as an oxidase mimic for tumor chemo-catalytic therapy.

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          Abstract

          Conventional tumor chemotherapy is limited by its low therapeutic efficacy and side effects, which severely hold back its further application as a first-line agent in clinic. To improve the cure efficacy of cancer, nanozyme with enzyme-like activity has now been extensively investigated as a new strategy for tumor treatment. Herein, an anti-tumor platform based on manganese oxides (MnOx) modified poly (lactic-co-glycolic acid) (PLGA)@polydopamine (PDA) nanoparticles (PP-MnOx NPs) as an oxidase mimic was developed. PP-MnOx NPs could not only produce abundant reactive oxygen species to inhibit tumor growth taking advantage of their oxidase-like activity, but also encapsulate and release antitumor drug (artesunate) to function as chemotherapy, achieving remarkable synergistic chemo-catalytic therapeutic effects. As an oxidase mimics, PP-MnOx NPs induced the decrease of mitochondrial membrane potential, down-regulation of Bcl-2, as well as activation of Bax and Caspase-3, demonstrating that the apoptosis triggered by PP-MnOx NPs was mediated via mitochondrial pathways. Importantly, the artesunate in PP-MnOx NPs further promoted this apoptosis. In addition, Mn ions released from PP-MnOx NPs facilitated the tumor-microenvironment-specific T1-weighted magnetic resonance imaging. Taken together, this study well clarifies the antitumor mechanism of artesunate-loaded PP-MnOx NPs and offer a synergistic chemo-catalytic strategy for tumor theranostics.

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          Author and article information

          Journal
          Int J Biol Macromol
          International journal of biological macromolecules
          Elsevier BV
          1879-0003
          0141-8130
          Jun 30 2021
          : 181
          Affiliations
          [1 ] Institute of Translational Medicine, Department of Pharmacology, School of Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, Jiangsu 225009, China.
          [2 ] Institute of Translational Medicine, Department of Pharmacology, School of Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China.
          [3 ] CAS Engineering Laboratory for Nanozyme, Institute of Biophysis, Chinese Academy of Sciences, Beijing 100101, China.
          [4 ] School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, Jiangsu 225002, China. Electronic address: fanlei@yzu.edu.cn.
          [5 ] Department of Cardiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China. Electronic address: qianxiaodong@suda.edu.cn.
          Article
          S0141-8130(21)00659-0
          10.1016/j.ijbiomac.2021.03.124
          33771546
          44ed6a06-020d-406a-8a4c-17a1e18f1e99
          Copyright © 2021 Elsevier B.V. All rights reserved.
          History

          MnO(x) modified PLGA/polydopamine nanoparticles,Chemo-catalytic tumor therapy,Oxidase,Reactive oxygen species

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