胶束
阿霉素
内化
拉帕蒂尼
结合
生物物理学
细胞外
药理学
材料科学
化学
癌症研究
化疗
细胞
医学
癌症
生物化学
乳腺癌
水溶液
有机化学
生物
曲妥珠单抗
内科学
数学分析
数学
作者
Zhihao Guo,Enhui Liang,Junhui Sui,Mengcheng Ma,Liqun Yang,Jiwei Wang,Jianshe Hu,Yong Sun,Yujiang Fan
标识
DOI:10.1016/j.actbio.2020.09.051
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.
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