机构:[a]Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China[b]Department of Anesthesiology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China诊疗科室麻醉科首都医科大学附属天坛医院[c]Department of Diagnostic Ultrasound, Beijing Tongren Hospital, Capital Medical University, Dong-Jiao-Min-Xiang, Dong Cheng District, Beijing 100730, China医技科室超声科首都医科大学附属同仁医院[d]State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin 300071, China[e]Department of Biomedical Engineering, University of Minnesota, 7-116 Hasselmo Hall, 312 Church Street S.E, Minneapolis, MN 55455, USA
The combination of chemotherapy and photothermal therapy in multifunctional nanovesicles has emerged as a promising strategy to improve cancer therapeutic efficacy. Herein, we designed new pH/reduction dual-responsive and folate decorated polymeric micelles (FA Co-PMs) as theranostic nanocarrier to co-encapsulate doxorubicin (DOX) and indocyanine green (ICG) for targeted NIR imaging and chemo-photothermal combination therapy. The Co-PMs exhibited nano-sized structure (similar to 100 nm) with good monodispersity, high encapsulation efficiency of both ICG and DOX, triggered DOX release in response to acid pH and reduction environment, and excellent temperature conversion with laser irradiation. In vitro cellular uptake study indicated FA Co-PMs achieved significant targeting to BEL-7404 cells via folate receptor-mediated endocytosis, and laser-induced hyperthermia further enhanced drug accumulation into cancer cells. In vivo biodistribution study indicated that FA Co-PMs prolonged drug circulation and enhanced drug accumulation into the tumor via EPR effect and FA targeting. Furthermore, the ICG-based photo-triggered hyperthermia combined with DOX-based chemotherapy synergistically induced the BEL-7404 cell death and apoptosis, and efficiently suppressed the BEL-7404 xenografted tumor growth while significantly reduced systemic toxicity in vivo. Therefore, the designed dual-responsive Co-PMs were promising theranostic nanocarriers for versatile antitumor drug delivery and imaging-guided cancer chemo-photothermal combination therapy. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81671806, 81571793, 31670948, 81671694]; CAMS Initiative for Innovative Medicine [2017-I2M-4-001, 2017-I2M-3-020]; Beijing Municipal Natural Science FoundationBeijing Natural Science Foundation [7172072]; Tianjin Municipal Natural Science FoundationNatural Science Foundation of Tianjin [15JCZDJC38300, 15JCQNJC46200]; Science and Technology Support Program of Tianjin [14RCGFSY00146]; Program for Innovative Research Team in Peking Union Medical College; Science Foundation for The Youth Teachers of Peking Union Medical College [2014zlgc0754]; Scientific Research Foundation of the State Human Resource Ministry; Education Ministry for Returned Chinese Scholars
第一作者机构:[a]Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China
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通讯作者:
通讯机构:[a]Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China