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基于聚三亚甲基碳酸酯/聚己内酯(共)聚物、鞣酸和阿霉素的可生物降解纳米粒的微流控辅助相分离法制备及其用于癌症治疗。

Microfluidic-assisted nanoprecipitation of biodegradable nanoparticles composed of PTMC/PCL (co)polymers, tannic acid and doxorubicin for cancer treatment.

机构信息

Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363, Lodz, Poland.

Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363, Lodz, Poland.

出版信息

Colloids Surf B Biointerfaces. 2021 May;201:111598. doi: 10.1016/j.colsurfb.2021.111598. Epub 2021 Feb 2.

Abstract

This study was aimed towards the development of a novel microfluidic approach for the preparation of (co)polymeric and hybrid nanoparticles (NPs) composed of (co)polymers/tannic acid (TA) in the microfluidic flow-focusing glass-capillary device. The MiliQ water was used as water phase, whereas the organic phase was composed of poly(ε-caprolactone) (PCL) and poly(trimethylene carbonate) (PTMC) homopolymers and (co)polymers with different proportion of comonomers which were prepared via enzymatic polymerization that allows avoiding the usage of potentially toxic catalyst. To prepare hybrid NPs, TA was additionally added to the organic phase. Subsequently, as a result of mixing between these distinct phases in microfluidic channels, the nanoprecipitation in the form of spherical NPs occurs. The size of NPs was tuned over the range of 140-230 nm by controlling phase flow rates and the composition of NPs. Moreover, the release studies of the encapsulated anticancer drug doxorubicin (DOX) demonstrated that the drug release is greatly influenced by the (co)polymers composition, their molecular weight, NPs size, and the presence of TA. The antitumor activities of the (co)polymeric and hybrid NPs toward breast cancer cells (MCF-7) were tested in vitro. Among all tested formulation, the NPs composed of PCL/TA most efficiently inhibit the cell proliferation of MCF-7 cells, most importantly, their efficiency was higher than free DOX. The proposed strategy may provide an efficient alternative for the construction of nanocarriers with great potential in anticancer therapy.

摘要

本研究旨在开发一种新颖的微流控方法,用于在微流控流聚焦玻璃毛细管装置中制备由(共)聚合物/单宁酸(TA)组成的(共)聚合物和杂化纳米颗粒(NPs)。MiliQ 水用作水相,而有机相由聚(ε-己内酯)(PCL)和聚(三亚甲基碳酸酯)(PTMC)均聚物以及通过酶聚合制备的具有不同比例单体的(共)聚合物组成,这可以避免使用潜在有毒催化剂。为了制备杂化 NPs,还将 TA 添加到有机相中。随后,由于这些不同相在微流道中混合,以球形 NPs 的形式发生纳米沉淀。通过控制相流速和 NPs 的组成,可将 NPs 的尺寸调谐在 140-230nm 范围内。此外,封装抗癌药物阿霉素(DOX)的释放研究表明,药物释放受(共)聚合物组成、分子量、NPs 尺寸和 TA 的存在的极大影响。(共)聚合物和杂化 NPs 对乳腺癌细胞(MCF-7)的体外抗肿瘤活性进行了测试。在所有测试配方中,由 PCL/TA 组成的 NPs 最有效地抑制 MCF-7 细胞的增殖,最重要的是,它们的效率高于游离 DOX。该策略可能为构建在抗癌治疗中具有巨大潜力的纳米载体提供一种有效的替代方法。

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