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可细胞内化且可在细胞内降解的阳离子聚氨酯胶束作为高效成像和药物递送的潜在平台。

Cell internalizable and intracellularly degradable cationic polyurethane micelles as a potential platform for efficient imaging and drug delivery.

作者信息

Ding Mingming, Zeng Xin, He Xueling, Li Jiehua, Tan Hong, Fu Qiang

机构信息

College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University , Chengdu 610065, China.

出版信息

Biomacromolecules. 2014 Aug 11;15(8):2896-906. doi: 10.1021/bm500506v. Epub 2014 Jul 15.

Abstract

A cell internalizable and intracellularly degradable micellar system, assembled from multiblock polyurethanes bearing cell-penetrating gemini quaternary ammonium pendent groups in the side chain and redox-responsive disulfide linkages throughout the backbone, was developed for potential magnetic resonance imaging (MRI) and drug delivery. The nanocarrier is featured as a typical "cleavable core-internalizable shell-protective corona" architecture, which exhibits small size, positive surface charge, high loading capacity, and reduction-triggered destabilization. Furthermore, it can rapidly enter tumor cells and release its cargo in response to an intracellular level of glutathione, resulting in enhanced drug efficacy in vitro. The magnetic micelles loaded with superparamagnetic iron oxide (SPIO) nanoparticles demonstrate excellent MRI contrast enhancement, with T2 relaxivity found to be affected by the morphology of SPIO-clustering inside the micelle core. The multifunctional carrier with good cytocompatibility and nontoxic degradation products can serve as a promising theranostic candidate for efficient intracellular delivery of anticancer drugs and real-time monitoring of therapeutic effect.

摘要

一种可细胞内化且可在细胞内降解的胶束系统被开发出来,用于潜在的磁共振成像(MRI)和药物递送。该系统由多嵌段聚氨酯组装而成,侧链带有细胞穿透性双子季铵侧基,主链贯穿氧化还原响应性二硫键。这种纳米载体具有典型的“可裂解核心-可细胞内化外壳-保护性冠层”结构,具有尺寸小、表面带正电荷、载药量高以及还原触发的不稳定等特点。此外,它能迅速进入肿瘤细胞,并根据细胞内谷胱甘肽水平释放其所载物质,从而在体外提高药物疗效。负载超顺磁性氧化铁(SPIO)纳米颗粒的磁性胶束表现出优异的MRI造影增强效果,T2弛豫率受胶束核心内SPIO聚集形态的影响。这种具有良好细胞相容性和无毒降解产物的多功能载体可作为一种有前景的诊疗候选物,用于高效的细胞内抗癌药物递送和治疗效果的实时监测。

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