Department of Chemical and Biomolecular Engineering, University of Melbourne, Parkville, Melbourne, VIC 3010, Australia.
Biomacromolecules. 2011 Oct 10;12(10):3469-77. doi: 10.1021/bm200604h. Epub 2011 Sep 2.
Amino acid-based core cross-linked star (CCS) polymers (poly(L-lysine)(arm)poly(L-cystine)(core)) with peripheral allyl functionalities were synthesized by sequential ring-opening polymerization (ROP) of amino acid N-carboxyanhydrides (NCAs) via the arm-first approach, using N-(trimethylsilyl)allylamine as the initiator. Subsequent functionalization with a poly(ethylene glycol) (PEG)-folic acid conjugate via thiol-ene click chemistry afforded poly(PEG-b-L-lysine)(arm)poly(L-cystine)(core) stars with outer PEG coronas decorated with folic acid targeting moieties. Similarly, a control was prepared without folic acid, using just PEG. A fluorophore was used to track both star polymers incubated with breast cancer cells (MDA-MB-231) in vitro. Confocal microscopy and flow cytometry revealed that the stars could be internalized into the cells, and higher cell internalization was observed when folic acid moieties were present. Cytotoxicity studies indicate that both stars are nontoxic to MDA-MB-231 cells at concentrations of up to 50 μg/mL. These results make this amino acid-based star polymer an attractive candidate in targeted drug delivery applications including chemotherapy.
具有周边烯丙基官能团的氨基酸基核交联星形（CCS）聚合物（聚（L-赖氨酸）（臂）聚（L-胱氨酸）（核））是通过氨基酸 N-羧酸酐（NCAs）的顺序开环聚合（ROP）通过臂首先方法合成的，使用 N-（三甲基甲硅烷基）烯丙胺作为引发剂。随后通过硫醇-烯点击化学与聚（乙二醇）（PEG）-叶酸缀合物进行功能化，得到了聚（PEG-b-L-赖氨酸）（臂）聚（L-胱氨酸）（核）星形聚合物，其外 PEG 冠上装饰有叶酸靶向部分。同样，仅使用 PEG 制备了没有叶酸的对照物。荧光团用于跟踪体外与乳腺癌细胞（MDA-MB-231）共孵育的两种星形聚合物。共焦显微镜和流式细胞术显示，星形聚合物可以被内化到细胞中，并且当存在叶酸部分时观察到更高的细胞内化。细胞毒性研究表明，两种星形聚合物在高达 50μg/mL 的浓度下对 MDA-MB-231 细胞均无毒性。这些结果使这种基于氨基酸的星形聚合物成为靶向药物递送应用（包括化学疗法）的有吸引力的候选物。
