Sulfobetaine polymers for effective permeability into multicellular tumor spheroids (MCTSs)
Sulfobetaine polymers for effective permeability into multicellular tumor spheroids (MCTSs)
复制标题
磺基甜菜碱聚合物可有效渗透至多细胞肿瘤球体 (MCTS)
DOI：
10.1039/d1tb02337c
复制
发表时间：
2022
影响因子：
7
通讯作者：
Yamamoto Masaya
中科院分区：
文献类型：
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作者：
Morimoto Nobuyuki;Ota Keisuke;Miura Yuki;Shin Heungsoo;Yamamoto Masaya
多细胞肿瘤球体（MCTS）是有吸引力的药物筛选动物试验前，因为他们模仿在体内的微环境。尽管药物可以穿透单层培养的细胞，但MCTS和肿瘤组织对候选药物的渗透性是不够的;因此，需要纳米载体来增强渗透性并递送药物。在这项研究中，我们制备了磺基甜菜碱甲基丙烯酸酯和（甲基）丙烯酰胺的两性离子聚合物，两性离子之间有或没有羟基，作为高渗透性的纳米载体。在磺基甜菜碱聚合物中，聚（2-羟基-3-（（3-甲基丙烯酰胺丙基）二甲基铵基）丙烷-1-磺酸酯），P（OH-MAAmSB），含羟基的甲基丙烯酰胺聚合物对单层培养的细胞表现出很小的细胞毒性和膜移位能力。P（OH-MAAmSB）具有良好的渗透性，能在150 s左右渗透到MCTS的中心区域（直径约325 μm），而阳离子聚合物聚（三甲基-2-甲基丙烯酰氧乙基铵）仅从外周渗透1 ~ 2层。P（OH-MAAmSB）的上级渗透性可能与其良好的溶解性和侧链构象有关。P（OH-MAAmSB）是一种很有前途的具有膜转运和渗透性的纳米载体。
Multicellular tumor spheroids (MCTSs) are attractive for drug screening before animal tests because they emulate an in vivo microenvironment. The permeability of the MCTSs and tumor tissues towards the candidate drugs is not sufficient even though the drugs can penetrate monolayer cultured cells; therefore, nanocarriers are required to enhance permeability and deliver drugs. In this study, we prepared zwitterionic polymers of sulfobetaine methacrylates and (meth)acrylamides with or without hydroxy groups between the zwitterions to serve as highly permeable nanocarriers. In the sulfobetaine polymers, poly(2-hydroxy-3-((3-methacrylamidopropyl)dimethylammonio)propane-1-sulfonate), P(OH–MAAmSB), the hydroxy group containing methacrylamide polymer exhibited little cytotoxicity and membrane translocation ability against monolayer cultured cells. Moreover, the excellent permeability of the hepatocyte MCTS enabled P(OH–MAAmSB) to permeate it and reach the center region (∼325 μm in diameter) at approximately 150 s, although poly(trimethyl-2-methacroyloxyethylammonium), a cationic polymer, penetrated just 1 to 2 layers from the periphery. The superior permeability of P(OH–MAAmSB) might be due to its good solubility and side chain conformation. P(OH–MAAmSB) is a promising nanocarrier with membrane translocation and permeability.