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温敏性壳聚糖-金杂化纳米粒子作为厄洛替尼的纳米载体。

Thermo-sensitive chitosan copolymer-gold hybrid nanoparticles as a nanocarrier for delivery of erlotinib.

机构信息

Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.

Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Int J Biol Macromol. 2018 Jan;106:266-276. doi: 10.1016/j.ijbiomac.2017.08.020. Epub 2017 Aug 9.

Abstract

Here, using (poly(N-isopropylacrylamide)-co-oleic acid)-g-chitosan ((PNIPAAm-co-OA)-g-CS), CS copolymer-gold hybrid nanoparticles (CGH NPs) were synthesized by autoreduction of auric cations (HAuCl) in aqueous solution in the absence of any other reducing agent. The engineered thermo-sensitive CS copolymer with free amino groups could reduce auric cations and stabilized the resultant NPs. CGH NPs were prepared using different concentrations of CS copolymer (0.1-1% w/v) and HAuCl (50-500μL, 0.2% w/v). They were characterized in terms of structure, surface Plasmon band, zeta potential, atomic absorption, stability, size and size distribution. The obtained CGH NPs showed a size range of 80-100nm and high stability at different pHs with no observable agglomeration/sedimentation for couple of months. The loading efficiency of erlotinib (ETB) in the CGH NPs was about 30%. The ETB was released from the CGH NPs in a thermo-responsive manner. FACS flow cytometry analysis confirmed high cellular uptake (85.81%) of CGH NPs by A549 cells. The cytotoxicity evaluations proved the cytocompatibility and high anti-tumor effect of the engineered CGH NPs. Based on these findings, having used thermo-sensitive CS copolymer, CGH NPs were obtained in one-pot procedure, which could be considered as stimuli-responsive delivery system with potential biomedical applications.

摘要

在这里,使用(聚(N-异丙基丙烯酰胺)-co-油酸)-g-壳聚糖((PNIPAAm-co-OA)-g-CS),通过在没有任何其他还原剂的情况下在水溶液中自还原金阳离子(HAuCl)合成了壳聚糖共聚物-g-金杂化纳米粒子(CGH NPs)。具有游离氨基的工程热敏性 CS 共聚物可以还原金阳离子并稳定所得 NPs。CGH NPs 是使用不同浓度的 CS 共聚物(0.1-1%w/v)和 HAuCl(50-500μL,0.2%w/v)制备的。它们的结构、表面等离子体带、zeta 电位、原子吸收、稳定性、尺寸和尺寸分布进行了表征。所得 CGH NPs 的粒径范围为 80-100nm,在不同 pH 值下具有高稳定性,在几个月内没有观察到聚集/沉淀。CGH NPs 中厄洛替尼(ETB)的载药效率约为 30%。CGH NPs 以热响应方式释放 ETB。FACS 流式细胞术分析证实 A549 细胞对 CGH NPs 的摄取率高达 85.81%。细胞毒性评价证明了工程 CGH NPs 的细胞相容性和高抗肿瘤作用。基于这些发现,使用热敏性 CS 共聚物,一锅法得到 CGH NPs,可作为具有潜在生物医学应用的刺激响应性递药系统。

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