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自组装丝胶蛋白/泊洛沙姆纳米颗粒作为疏水性和亲水性药物的靶向递送纳米载体

Self-assembled silk sericin/poloxamer nanoparticles as nanocarriers of hydrophobic and hydrophilic drugs for targeted delivery.

作者信息

Mandal Biman B, Kundu S C

机构信息

Department of Biotechnology, Indian Institute of Technology, Kharagpur, India.

出版信息

Nanotechnology. 2009 Sep 2;20(35):355101. doi: 10.1088/0957-4484/20/35/355101. Epub 2009 Aug 11.

Abstract

In recent times self-assembled micellar nanoparticles have been successfully employed in tissue engineering for targeted drug delivery applications. In this review, silk sericin protein from non-mulberry Antheraea mylitta tropical tasar silk cocoons was blended with pluronic F-127 and F-87 in the presence of solvents to achieve self-assembled micellar nanostructures capable of carrying both hydrophilic (FITC-inulin) and hydrophobic (anticancer drug paclitaxel) drugs. The fabricated nanoparticles were subsequently characterized for their size distribution, drug loading capability, cellular uptake and cytotoxicity. Nanoparticle sizes ranged between 100 and 110 nm in diameter as confirmed by dynamic light scattering. Rapid uptake of these particles into cells was observed in in vitro cellular uptake studies using breast cancer MCF-7 cells. In vitro cytotoxicity assay using paclitaxel-loaded nanoparticles against breast cancer cells showed promising results comparable to free paclitaxel drugs. Drug-encapsulated nanoparticle-induced apoptosis in MCF-7 cells was confirmed by FACS and confocal microscopic studies using Annexin V staining. Up-regulation of pro-apoptotic protein Bax, down-regulation of anti-apoptotic protein Bcl-2 and cleavage of regulatory protein PARP through Western blot analysis suggested further drug-induced apoptosis in cells. This study projects silk sericin protein as an alternative natural biomaterial for fabrication of self-assembled nanoparticles in the presence of poloxamer for successful delivery of both hydrophobic and hydrophilic drugs to target sites.

摘要

近年来,自组装胶束纳米颗粒已成功应用于组织工程中的靶向药物递送。在本综述中,将非桑蚕丝柞蚕热带柞蚕丝茧中的丝胶蛋白与普朗尼克F - 127和F - 87在溶剂存在下混合,以实现能够携带亲水性(异硫氰酸荧光素 - 菊粉)和疏水性(抗癌药物紫杉醇)药物的自组装胶束纳米结构。随后对制备的纳米颗粒进行了尺寸分布、载药能力、细胞摄取和细胞毒性的表征。通过动态光散射确认,纳米颗粒直径在100至110纳米之间。在使用乳腺癌MCF - 7细胞的体外细胞摄取研究中,观察到这些颗粒能快速被细胞摄取。使用载有紫杉醇的纳米颗粒对乳腺癌细胞进行的体外细胞毒性试验显示出与游离紫杉醇药物相当的有前景的结果。通过使用膜联蛋白V染色的流式细胞术和共聚焦显微镜研究证实了载药纳米颗粒诱导MCF - 7细胞凋亡。通过蛋白质印迹分析,促凋亡蛋白Bax的上调、抗凋亡蛋白Bcl - 2的下调以及调节蛋白PARP的裂解表明细胞中进一步发生了药物诱导的凋亡。本研究将丝胶蛋白作为一种替代性天然生物材料,用于在泊洛沙姆存在下制备自组装纳米颗粒,以成功地将疏水性和亲水性药物递送至靶位点。

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