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pH-triggered intracellular release from actively targeting polymer micelles

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WOS被引频次:135
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成果类型:
期刊论文
作者:
Guo, Xing;Shi, Chunli;Wang, Jie;Di, Shubin;Zhou, Shaobing*
通讯作者:
Zhou, Shaobing
作者机构:
[Di, Shubin; Guo, Xing; Zhou, Shaobing; Wang, Jie] Southwest Jiaotong Univ, Sch Mat Sci & Engn, Minist Educ, Key Lab Adv Technol Mat, Chengdu 610031, Peoples R China.
[Shi, Chunli] Southwest Jiaotong Univ, Sch Life Sci & Engn, Chengdu 610031, Peoples R China.
通讯机构:
[Zhou, Shaobing] Southwest Jiaotong Univ, Sch Mat Sci & Engn, Minist Educ, Key Lab Adv Technol Mat, Chengdu 610031, Peoples R China.
语种:
英文
关键词:
Nanotechnology;Polymeric micelle;Drug delivery;Tumor targeting;pH-sensitive
期刊:
Biomaterials
ISSN:
0142-9612
年:
2013
卷:
34
期:
18
页码:
4544-4554
文献类别:
WOS:Article;EI:Journal article (JA)
所属学科:
ESI学科类别:材料科学;WOS学科类别:Engineering, Biomedical;Materials Science, Biomaterials
入藏号:
WOS:000317884800014;EI:20131416176036
基金类别:
National Basic Research Program of China (973 Program) [2012CB933600]; National Natural Science Foundation of China [30970723, 51173150]
机构署名:
本校为第一且通讯机构
院系归属:
材料科学与工程学院
生命科学与工程学院
摘要:
Chemotherapy is widely applied to treat cancer patients but its application is limited due to the systemic toxicity and low efficacy. Nanocarrier system, which is capable of delivering their toxic cargos specifically into cancer cells and then greatly overcomes these disadvantages, has drawn a broad attention. Here we developed a drug-conjugated micelle for a better drug delivery in which folic acid was attached to the DOX-conjugated poly(ethylene glycol)-poly(epsilon-caprolactone) to target tumor; DOX was further connected with a hydrazone linker (FA-hyd) for a pH-triggered drug release. Comparing to other DOX-conjugated micelles either linked with carbamate (FA-cbm) or lacking FA(m-hyd), the developed FA-hyd demonstrated excellent biocompatibility; When analyzed with Alamar blue assays, flow cytometry and confocal laser scanning microscopy (CLSM), the pH-sensitive FA-functionalized DOX-conjugated micelles presented much better efficiency of cellular uptake and higher cytotoxicity to tumor cells. In vivo pharmacokinetics and biodistribution studies indicated that FA-hyd micelles significantly prolonged the blood circulation time of drug and enriched drug into the tumors rather than normal tissues. In vivo antitumor activity demonstrated that FA-hyd micelles had the highest safety to body and the best therapeutic efficacy to tumors. Therefore, this drug delivery system is deemed as a potential nanocarrier for cancer therapy. (C) 2013 Elsevier Ltd. All rights reserved.
参考文献:
Adair JH, 2010, ACS NANO, V4, P4967, DOI 10.1021/nn102324e
Ashley CE, 2011, NAT MATER, V10, P389, DOI [10.1038/NMAT2992, 10.1038/nmat2992]
Bae Y, 2003, ANGEW CHEM INT EDIT, V42, P4640, DOI 10.1002/anie.200250653
Barreto JA, 2011, ADV MATER, V23, pH18, DOI 10.1002/adma.201100140
Batrakova EV, 2005, BIOCONJUGATE CHEM, V16, P793, DOI 10.1021/bc049730c

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