A Transformable Amphiphilic and Block Polymer-Dendron Conjugate for Enhanced Tumor Penetration and Retention with Cellular Homeostasis Perturbation via Membrane Flow.
机构：[1]Huaxi MR Research Center (HMRRC), Animal Experimental Center, Department of Radiology, National Clinical Research Center for Geriatrics, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.四川大学华西医院[2]Department of Chemical Engineering, Imperial College London, South Kensington Campus, London, SW7 2AZ, United Kingdom.[3]Functional and Molecular Imaging Key Laboratory of Sichuan Province, and Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, 610041, China.[4]Amgen Bioprocessing Centre, Keck Graduate Institute, Claremont, CA, 91711, USA.
Efficient penetration and retention of therapeutic agents in tumor tissues can be realized through rational design of drug delivery systems. Herein, we present a polymer-dendron conjugate, POEGMA-b-p(GFLG-Dendron-Ppa) (GFLG-DP), which allows cathepsin B (CTSB)-triggered stealthy-to-sticky structural transformation. The compositions and ratios were optimized through dissipative particle dynamics simulations. GFLG-DP displayed tumor-specific transformation and consequently released dendron-Ppa was found to effectively accumulate on the tumor cell membrane. The interaction between dendron-Ppa and the tumor cell membrane resulted in intracellular and intercellular transport via membrane flow, thus achieving efficient deep penetration and prolonged retention of therapeutic agents in solid tumor tissues. Meanwhile, the interaction of dendron-Ppa with endoplasmic reticulum disrupted the cell homeostasis, making tumor cells more vulnerable and susceptible to the photodynamic therapy. This platform represents a versatile approach to augmenting the tumor therapeutic efficacy of a nanomedicine via manipulation of its interactions with tumor membrane systems. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.
基金：
Lei Gu and Zhenyu Duan contributed equally to this work. This work was supported by National
Natural Science Foundation of China (52073193, 51873120 and 81621003), 1‧3‧5 Project for
Disciplines of Excellence, West China Hospital, Sichuan University (ZYJC21013, ZYGD20007 and
ZYJC18011), Research Funds in West China Hospital of Sichuan University (2020HXBH072),
Science and Technology Program of Sichuan province (2020YJ0231) and China Postdoctoral Science
Foundation (2019TQ0220). Apanpreet Bhamra was supported by the Engineering and Physical
Sciences Research Council Doctoral Training Partnership (EPSRC DTP) Studentship. The authors
would like to thank the Analytical and Testing Center of Sichuan University for morphology
characterization work and the authors would be grateful to Guiping Yuan for her help of TEM images.
Thanks to Dr. Chunxia Wang from College of Chemistry, Sichuan University for technical assistance.
Thanks to Sisi Wu, Hongying Chen, Zhiqian Li, Xuemei Chen, Li Fu, Xiangyi Ren, Ping Liao, Bo Su
and Lin Bo (Research Core Facility, West China Hospital, Sichuan University) for their help in cell
studies and histological studies. Thanks to Xue Li, Qiaorong Huang and Wentong Meng (Laboratory
of Stem Cell Biology, West China Hospital, Sichuan University) for work in flow cytometer.
第一作者机构：[1]Huaxi MR Research Center (HMRRC), Animal Experimental Center, Department of Radiology, National Clinical Research Center for Geriatrics, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
通讯作者：
通讯机构：[1]Huaxi MR Research Center (HMRRC), Animal Experimental Center, Department of Radiology, National Clinical Research Center for Geriatrics, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.[3]Functional and Molecular Imaging Key Laboratory of Sichuan Province, and Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, 610041, China.
推荐引用方式(GB/T 7714)：
Gu Lei,Duan Zhenyu,Chen Xiaoting,et al.A Transformable Amphiphilic and Block Polymer-Dendron Conjugate for Enhanced Tumor Penetration and Retention with Cellular Homeostasis Perturbation via Membrane Flow.[J].Advanced materials (Deerfield Beach, Fla.).2022,34(16):e2200048.doi:10.1002/adma.202200048.
APA：
Gu Lei,Duan Zhenyu,Chen Xiaoting,Li Xiaoling,Luo Qiang...&Luo Kui.(2022).A Transformable Amphiphilic and Block Polymer-Dendron Conjugate for Enhanced Tumor Penetration and Retention with Cellular Homeostasis Perturbation via Membrane Flow..Advanced materials (Deerfield Beach, Fla.),34,(16)
MLA：
Gu Lei,et al."A Transformable Amphiphilic and Block Polymer-Dendron Conjugate for Enhanced Tumor Penetration and Retention with Cellular Homeostasis Perturbation via Membrane Flow.".Advanced materials (Deerfield Beach, Fla.) 34..16(2022):e2200048
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