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Lapatinib-loaded acidity-triggered charge switchable polycarbonate-doxorubicin conjugate micelles for synergistic breast cancer chemotherapy.

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机构: [a]Center for Molecular Science and Engineering, College of Science, Northeastern University, Shenyang, 110819, P. R. China [b]National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu, 610064, P. R. China [c]NHC Key Laboratory of Reproductive Health and Medical Genetics (Liaoning Research Institute of Family Planning), The Affiliated Reproductive Hospital of China Medical University, Shenyang, 110031, P. R. China [d]Fujian Province University Engineering Research Center of Mindong She Nationality Medicine, College of Chemistry and Materials, Ningde Normal University, Ningde, 352100, P. R. China
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关键词: Polycarbonates Charge switch Polymeric micelles Dual pH-responsive Synergistic chemotherapy

摘要:
Stimulus-responsive nanosystem is a powerful method to improve the bioavailability and reduce the side effects of anticancer agents. In the present study, a customized dual pH-responsive micellar nanoplatform (DOX+LAP-M) based on polycarbonate-doxorubicin conjugate micelles was prepared to co-deliver the chemotherapeutic agent lapatinib for inhibiting tumor growth and metastasis. DOX+LAP-M micelles with spherical morphology had a size of ~112 nm and had an initial negative surface charge, which are favorable characteristics for long-term circulation in the blood. Once the micelles accumulated in tumor tissues, the intrinsic tumor extracellular acidity triggered the charge switch of DOX+LAP-M micelles from -1 to 9 mV, thereby facilitating cell internalization and tumor penetration. Subsequently, the pH-sensitive micellar core accelerated the release of doxorubicin and lapatinib in the acidic intracellular environment. DOX+LAP-M micelles effectively inhibited the proliferation, migration, and invasion of 4T1 cells in vitro; furthermore, the administration of DOX+LAP-M micelles in 4T1 xenograft-bearing mice suppressed solid tumor growth with an inhibitory rate of 90.2% and significantly decreased pulmonary metastatic nodules, without significant systemic toxicity. This multifunctional micellar system has high potential for clinical cancer therapy. Copyright © 2020. Published by Elsevier Ltd.

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出版当年[2020]版:
大类 | 1 区 工程技术
小类 | 1 区 工程:生物医学 1 区 材料科学:生物材料
最新[2023]版:
大类 | 1 区 医学
小类 | 1 区 工程:生物医学 1 区 材料科学:生物材料
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第一作者机构: [a]Center for Molecular Science and Engineering, College of Science, Northeastern University, Shenyang, 110819, P. R. China [b]National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu, 610064, P. R. China
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