Institute for Materials Chemistry and Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
Biomacromolecules. 2022 Apr 11;23(4):1569-1580. doi: 10.1021/acs.biomac.1c01343. Epub 2022 Jan 28.
Selective targeting of specific cells without the use of biological ligands has not been achieved. In the present study, we revealed that the coacervate droplets formed from poly(2-methoxyethyl acrylate) (PMEA) and its derivatives selectively accumulated to tumor cells. PMEA derivatives, which are insoluble acrylate polymers, induced coacervation in water to form polymer-dense droplets via hydrophobic interaction. Interestingly, the accumulation of coacervate droplets to tumor cells was involved in the bound water content of PMEA derivatives. Coacervate droplets with a high bound water content accumulated and internalized up to 36.6-fold higher in HeLa cervical tumor cells than in normal human fibroblasts (NHDF). Moreover, the interactions between coacervate droplets and plasma membrane components such as CD44 played a key role in this accumulation process. Therefore, coacervate droplets formed from PMEA derivatives have great clinical potential in tumor cell detection, development of alternative tumor-targeting ligands, and optimization of drug delivery carriers.
目前，还没有实现不使用生物配体而选择性靶向特定细胞的目标。在本研究中，我们揭示了由聚（2-甲氧基乙酯）（PMEA）及其衍生物形成的凝聚液滴选择性地聚集到肿瘤细胞上。不溶于水的丙烯酸盐聚合物 PMEA 衍生物在水中通过疏水相互作用诱导凝聚形成聚合物致密液滴。有趣的是，凝聚液滴聚集到肿瘤细胞涉及到 PMEA 衍生物的结合水含量。具有高结合水含量的凝聚液滴在 HeLa 宫颈肿瘤细胞中的积累和内化量比正常人类成纤维细胞（NHDF）高 36.6 倍。此外，凝聚液滴与 CD44 等质膜成分之间的相互作用在这一积累过程中起着关键作用。因此，PMEA 衍生物形成的凝聚液滴在肿瘤细胞检测、替代肿瘤靶向配体的开发以及优化药物输送载体方面具有巨大的临床潜力。
