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Control of Mitochondrial Localization Using Thermoresponsive Sulfobetaine Polymer.
Macromolecular Bioscience ( IF 4.6 ) Pub Date : 2020-09-13 , DOI: 10.1002/mabi.202000205
Nobuyuki Morimoto 1 , Yoshifumi Oishi 1 , Masaya Yamamoto 1, 2
Affiliation  

Fast intracellular migration and controlled localization of molecules represent significant challenges for future applications of drug discovery and related fields. In this study, thermoresponsive sulfobetaine polymers with pyridinium cations are evaluated as biocompatible and mitochondria‐localizing agents. Among the polymers, poly(3‐(4‐(2‐methacrylamido)ethyl pyridinio‐1‐yl)propane‐1‐sulfonate), P(E‐PySMAAm)14k (Mn = 14 000 g mol−1) exhibit thermoresponsiveness with an upper critical solution temperature like behavior in cell culture medium containing serum with minimal cytotoxicity. Upon the addition of P(E‐PySMAAm)14k to HeLa cells at temperatures above the clearing point at 37 °C, effective localization is observed in mitochondria. However, increased intensity but nonspecific localization is observed below the clearing point at 4 °C. Doxorubicin is conjugated to the P(E‐PySMAAm) and achieves effective mitochondrial delivery while maintaining drug efficacy. Such sulfobetaine polymers represent promising tools for intracellular delivery of molecules.

中文翻译:

使用热反应性磺基甜菜碱聚合物控制线粒体定位。

快速的细胞内迁移和分子的受控定位代表了药物发现和相关领域未来应用的重大挑战。在这项研究中,具有吡啶鎓阳离子的热响应性磺基甜菜碱聚合物被评估为生物相容性和线粒体定位剂。在聚合物中,聚(3-(4-(2-甲基丙烯酰胺)乙基吡啶-1-基)丙烷-1-磺酸盐),P(E-PySMAAm)14k(M n  = 14 000 g mol -1) 在含有最低细胞毒性的血清的细胞培养基中表现出具有较高临界溶液温度的热响应性,类似于行为。在高于清除点 37°C 的温度下将 P(E-PySMAAm)14k 添加到 HeLa 细胞后,在线粒体中观察到有效定位。然而,在 4 °C 的清点以下观察到强度增加但非特异性定位。多柔比星与 P(E-PySMAAm) 结合,实现有效的线粒体递送,同时保持药物疗效。这种磺基甜菜碱聚合物代表了用于细胞内分子递送的有前途的工具。
更新日期:2020-09-13
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