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一种基于 pH 响应聚合物胶束的可用于癌症识别的 MRI 对比剂。

A cancer-recognizable MRI contrast agents using pH-responsive polymeric micelle.

机构信息

Department of Biotechnology, The Catholic University of Korea, 43 Jibong ro, Wonmi-gu, Bucheon-si, Gyeonggi do 420-743, Republic of Korea.

出版信息

Biomaterials. 2014 Jan;35(1):337-43. doi: 10.1016/j.biomaterials.2013.10.004. Epub 2013 Oct 15.

Abstract

A cancer-recognizable MRI contrast agents (CR-CAs) has been developed using pH-responsive polymeric micelles. The CR-CAs with pH sensitivity were self-assembled based on well-defined amphiphilic block copolymers, consisting of methoxy poly(ethylene glycol)-b-poly(L-histidine) (PEG-p(L-His)) and methoxy poly(ethylene glycol)-b-poly(L-lactic acid)-diethylenetriaminopentaacetic acid dianhydride-gadolinium chelate (PEG-p(L-LA)-DTPA-Gd). The CR-CAs have a spherical shape with a uniform size of ~40 nm at physiological pH (pH 7.4). However, in acidic tumoral environment (pH 6.5), the CR-CAs were destabilized due to the protonation of the imidazole groups of p(L-His) blocks, causing them to break apart into positively charged water-soluble polymers. As a result, the CR-CAs exhibit highly effective T1 MR contrast enhancement in the tumor region, which enabled the detection of small tumors of ~3 mm(3 )in vivo at 1.5 T within a few minutes.

摘要

一种基于 pH 响应性聚合物胶束的肿瘤可识别 MRI 对比剂(CR-CAs)已被开发出来。这些具有 pH 敏感性的 CR-CAs 是基于结构明确的两亲性嵌段共聚物自组装而成的,共聚物由甲氧基聚(乙二醇)-b-聚(L-组氨酸)(PEG-p(L-His))和甲氧基聚(乙二醇)-b-聚(L-乳酸)-二亚乙基三胺五乙酸二酐-钆螯合物(PEG-p(L-LA)-DTPA-Gd)组成。在生理 pH 值(pH 7.4)下,CR-CAs 呈现出球形,粒径均匀,约为 40nm。然而,在酸性肿瘤环境(pH 6.5)下,由于 p(L-His)嵌段中咪唑基团的质子化,CR-CAs 会变得不稳定,导致其分解成带正电荷的水溶性聚合物。因此,CR-CAs 在肿瘤区域表现出高效的 T1 磁共振对比增强,能够在 1.5T 下在几分钟内检测到体内约 3mm3 的小肿瘤。

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