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介孔硅纳米载体的 pH 响应性药物传递系统用于提高紫杉醇的抗癌疗效

Microfluidic Synthesis of Lignin/Chitosan Nanoparticles for the pH-Responsive Delivery of Anticancer Drugs.

机构信息

Chemical Engineering Research Center, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, P. R. China.

State Key Laboratory of Chemical Engineering, Tianjin University, Tianjin 300072, P. R. China.

出版信息

Langmuir. 2021 Jun 15;37(23):7219-7226. doi: 10.1021/acs.langmuir.1c00778. Epub 2021 Jun 2.

DOI:10.1021/acs.langmuir.1c00778
PMID:34078082
Abstract

In this work, lignin/chitosan nanoparticles (Lig/Chi NPs) with controlled structures were synthesized in a simple and scalable microfluidic system. When the positively charged chitosan and the negatively charged lignin solution were blended in a microreactor, Lig/Chi NPs were rapidly formed via the electrostatic coassembly between the amino groups of chitosan and the carboxyl groups of lignin. The ζ potential changes from negative (-13 mV) to positive (+54.5 mV) for Lig NPs and Lig/Chi NPs, respectively. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) results demonstrated that Lig/Chi NPs have an average particle size of about 180 nm, which can be used as nanocarriers for drug delivery. The anticancer drug nanoparticles with docetaxel (DTX) and curcumin (CCM) were prepared by coassembly with Lig/Chi NPs in a microreactor, which had good drug loading efficiency, biocompatibility, and can release drugs in response to pH in the weakly acidic environment of the tumor. The drug release amounts in acidic solutions that simulated the tumor microenvironment were 51% (DTX@Lig/Chi NPs) and 50% (CCM@Lig/Chi NPs), respectively, which were better than the release amounts at pH 7.4, and have an obvious killing effect on HeLa cells.

摘要

在这项工作中,采用简单且可扩展的微流控系统合成了具有可控结构的木质素/壳聚糖纳米颗粒(Lig/Chi NPs)。当带正电荷的壳聚糖和带负电荷的木质素溶液在微反应器中混合时,通过壳聚糖的氨基与木质素的羧基之间的静电共组装,迅速形成 Lig/Chi NPs。Lig NPs 和 Lig/Chi NPs 的 ζ 电位分别从负(-13 mV)变为正(+54.5 mV)。扫描电子显微镜(SEM)和透射电子显微镜(TEM)结果表明,Lig/Chi NPs 的平均粒径约为 180nm,可作为药物传递的纳米载体。通过在微反应器中与 Lig/Chi NPs 共组装,制备了载有抗癌药物多西紫杉醇(DTX)和姜黄素(CCM)的纳米颗粒,具有良好的载药效率、生物相容性,并能响应肿瘤弱酸性环境中的 pH 值释放药物。在模拟肿瘤微环境的酸性溶液中的药物释放量分别为 51%(DTX@Lig/Chi NPs)和 50%(CCM@Lig/Chi NPs),均优于 pH7.4 时的释放量,对 HeLa 细胞具有明显的杀伤作用。

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