pH-Sensitive Delivery Vehicle Based on Folic Acid-Conjugated Polydopamine-Modified Mesoporous Silica Nanoparticles for Targeted Cancer Therapy

pH-Sensitive Delivery Vehicle Based on Folic Acid-Conjugated Polydopamine-Modified Mesoporous Silica Nanoparticles for Targeted Cancer Therapy
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DOI:
10.1021/acsami.7b02457
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发表时间:
2017-06-07
影响因子:
9.5
通讯作者:
Zeng, Xiaowei
Zeng, Xiaowei
中科院分区:
材料科学2区
文献类型:
--
作者:
Cheng, Wei;Nie, Junpeng;Zeng, Xiaowei

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在本研究中,我们在聚氯帕丁(PDA)修饰的介孔二氧化硅纳米颗粒(MSNs)表面靶向聚合物聚乙二醇叶酸(PEG FA),开发了新型纳米颗粒(NPs) MSNs@PDA-PEGHFA,并将其作为一种载多柔比星(DOX)的药物递送系统,作为宫颈癌治疗的模型药物。通过透射电子显微镜、x射线光电子能谱(N-2吸附/解吸)、动态光散射-自吸仪、热重分析和傅里叶变换红外光谱对NPs的化学结构和性质进行了表征。对ph值敏感的PDA涂层起到了守门人的作用。体外药物释放实验显示,ph依赖性和持续的药物释放谱可以增强抗癌治疗效果,并最大限度地减少肿瘤酸性微环境对正常细胞的潜在损害。这些MSN5@PDA-PEG-FA获得了显著的高靶向效率,这是由体外细胞摄取和细胞靶向实验证明。与不含叶酸靶向ligakl的游离DOX和负载DOX的NPs相比,fa靶向NPs在体内表现出更高的抗肿瘤效果,这意味着它们是一种极具潜力的癌症治疗载体。
In this study, we introduced,a targeting polymer poly(ethylene glycol) folic acid (PEG FA) on the surface of polyclopatnine (PDA)modified mesoporous silica nanoparticles (MSNs) to develop the novel nanoparticles (NPs) MSNs@PDA-PEGHFA, which were employed as a drug delivery system loaded with doxorubicin (DOX) as a model drug for cervical cancer therapy. The chemical structure and properties of these NPs were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy) N-2 adsorption/desorption, dynamic light scattering-autosizer, thermogravimetric analysis, and Fourier transform infrared spectroscopy. The pH-sensitive PDA coating served as a gatekeeper. The in vitro drug release experiments showed pH-dependent and 'sustained drug,release profiles that could enhance the therapeutic anticancer effect and minimize potential damage to normal cells due to the acidic microenvironment of theitumor. These MSN5@PDA-PEG-FA achieved significantly high targeting efficiency, which was demonstrated by the in vitro Cellular uptake and cellular targeting assay. Compared with that of free DOX and DOX, loaded NPs without the folic targeting ligakl, the FA-targeted NPs exhibited higher antitumor efficky in vivo) implying that they are a highly promising potential carrier for cancer treatments.