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无定形紫杉醇在介孔赤铁矿纳米棒中的高效负载及其体外抗肿瘤活性。

Highly efficient loading of amorphous paclitaxel in mesoporous hematite nanorods and their in vitro antitumor activity.

作者信息

Wu Ming, Xia Xi-Ming, Cui Can, Yu Ping, Zhang Yang, Liu Lei, Zhuo Ren-Xi, Huang Shi-Wen

机构信息

Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China.

出版信息

J Mater Chem B. 2013 Mar 28;1(12):1687-1695. doi: 10.1039/c3tb00472d. Epub 2013 Feb 5.

Abstract

Porous hematite nanorods (PHNRs) are potential candidates as drug delivery carriers because of their pores which are available for the encapsulation of drugs and genes, large surface area for loading biomacromolecules, biocompatibility, storage stability and inexpensive large-scale preparation. We report a facile synthesis of PHNRs loaded with a poorly water-soluble drug, paclitaxel (PTX). PHNRs were used as templates for the precipitation of PTX in a dimethyl sulfoxide (DMSO)-water mixture. The precipitation of amorphous PTX in the pores of PHNRs was characterized by nitrogen adsorption-desorption analysis, differential thermal analysis (DTA) and fourier transform infrared spectroscopy (FT-IR). Thermogravimetric analysis (TGA) and ultraviolet-visible (UV-vis) measurements determined that the loading of paclitaxel in PHNRs was high (17.6 wt%) and that the loading efficiency was up to 96%. We further studied the effect of free PTX or PTX-loaded PHNRs on the growth inhibition of HeLa cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and live/dead staining. PTX-loaded PHNRs showed significant cytotoxicity to HeLa cells. However, the ability of PTX-loaded PHNRs to inhibit cell growth was slightly lower or similar to that of free PTX after 48 h incubation. Confocal laser scanning microscopy (CLSM) and flow cytometric analysis suggested that HeLa cell death induced by free PTX or PTX-loaded PHNRs occurred via apoptosis, which was detected by Annexin V antibody and propidium iodide staining.

摘要

多孔赤铁矿纳米棒(PHNRs)因其具有可用于包封药物和基因的孔隙、用于负载生物大分子的大表面积、生物相容性、储存稳定性以及廉价的大规模制备方法,而成为药物递送载体的潜在候选材料。我们报道了一种简便的方法来合成负载难溶性药物紫杉醇(PTX)的PHNRs。PHNRs被用作模板,在二甲基亚砜(DMSO)-水混合物中沉淀PTX。通过氮吸附-脱附分析、差示热分析(DTA)和傅里叶变换红外光谱(FT-IR)对PHNRs孔隙中无定形PTX的沉淀进行了表征。热重分析(TGA)和紫外-可见(UV-vis)测量确定PHNRs中紫杉醇的负载量很高(17.6 wt%),负载效率高达96%。我们进一步通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)法和活/死染色研究了游离PTX或负载PTX的PHNRs对HeLa细胞生长抑制的影响。负载PTX的PHNRs对HeLa细胞显示出显著的细胞毒性。然而,孵育48小时后,负载PTX的PHNRs抑制细胞生长的能力略低于游离PTX或与之相似。共聚焦激光扫描显微镜(CLSM)和流式细胞术分析表明,游离PTX或负载PTX的PHNRs诱导的HeLa细胞死亡是通过凋亡发生的,这通过膜联蛋白V抗体和碘化丙啶染色检测到。

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