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载多西紫杉醇介孔磁性胶体纳米晶簇对体外膀胱癌 T24 细胞的抑制和凋亡作用。

The inhibitory and apoptotic effects of docetaxel-loaded mesoporous magnetic colloidal nanocrystal clusters on bladder cancer T24 cells in vitro.

出版信息

J Biomed Nanotechnol. 2014 Mar;10(3):455-62. doi: 10.1166/jbn.2014.1779.

Abstract

Mesoporous magnetic colloidal nanocrystal clusters (MCNCs) are featured with high magnetization, adequate surface area, excellent colloidal stability, good biocompatibility, and acid degradability. It is thus highly anticipated that MCNCs can serve as vehicles for target drug delivery. Herein, the mesoporous MCNCs stabilized by poly(gamma-glutamic acid) (PGA) were fabricated by the modified solvothermal route, showing a high specific surface area (126.4 m2/g), strong magnetic response (63 emu/g) and appropriate mesoporosity including a large pore volume (0.27 cm3/g) and accessible pore size (8.1 nm). Docetaxel (DOC) was then loaded in the resultant MCNCs using the nanoprecipitation method, and a high drug loading capacity was achieved up to 24 wt%. The chemotherapeutic effect and mechanism of DOC-MCNC conjugates in bladder cancer was evaluated in vitro. A series of analyses for cell uptake, cell viability, cell cycle, cell apoptosis and some cell proteins were performed by transmission electron microscopy, MTT assay, flow cytometry, cell nuclei staining, Annexin V staining assay, western blot assay and caspase-3 activity assay, respectively. The results demonstrated that DOC-MCNC conjugates enhanced the inhibitory effect by hampering mitoschisis and increased the apoptotic effect by changing the expression of apoptosis-related proteins in T24 cells, substantially proving their remarkable efficiency in treatment of bladder cancer.

摘要

介孔磁性胶体纳米晶簇(MCNCs)具有高磁化率、足够的比表面积、优异的胶体稳定性、良好的生物相容性和酸降解性。因此,人们高度期待 MCNCs 可以作为靶向药物传递的载体。在此,通过改进的溶剂热法制备了由聚(γ-谷氨酸)(PGA)稳定的介孔 MCNCs,其具有高比表面积(126.4 m2/g)、强磁响应(63 emu/g)和适当的介孔性,包括大孔体积(0.27 cm3/g)和可及的孔径(8.1 nm)。然后使用纳米沉淀法将多西他赛(DOC)载入所得的 MCNCs 中,实现了高达 24wt%的高载药量。通过透射电子显微镜、MTT 测定、流式细胞术、细胞细胞核染色、Annexin V 染色测定、Western blot 测定和 caspase-3 活性测定,分别对膀胱癌中 DOC-MCNC 缀合物的化疗效果和机制进行了评估。结果表明,DOC-MCNC 缀合物通过阻碍有丝分裂来增强抑制作用,并通过改变 T24 细胞中凋亡相关蛋白的表达来增加凋亡作用,充分证明了它们在膀胱癌治疗中的显著疗效。

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