Institut Galien Paris-Sud, Université Paris-Sud, UMR CNRS, Faculté de Pharmacie, Châtenay-Malabry, France.
Biomacromolecules. 2013 Aug 12;14(8):2837-47. doi: 10.1021/bm400657g. Epub 2013 Jul 18.
The synthesis of a novel class of polymer prodrug nanoparticles with anticancer activity is reported by using squalene, a naturally occurring isoprenoid, as a building block by the reversible addition-fragmentation (RAFT) technique. The RAFT agent was functionalized by gemcitabine (Gem) as anticancer drug, and the polymerization of squalenyl-methacrylate (SqMA) led to well-defined macromolecular prodrugs comprising one Gem at the extremity of each polymer chain. The amphiphilic nature of the resulting Gem-PSqMA conjugates allowed them to self-assemble into long-term stable and narrowly dispersed nanoparticles with significant anticancer activity in vitro on various cancer cell lines. To confer stealth properties on these nanoparticles, their PEGylation was successfully performed, as confirmed by X-ray photoelectron spectroscopy (XPS) and complement activation assay. It was also shown that the PEGylated nanoparticles could be internalized in cancer cells to a greater extent than their non-PEGylated counterparts.
本文报道了一类新型聚合物前药纳米粒子的合成，该纳米粒子具有抗癌活性，使用角鲨烯（一种天然的异戊二烯）作为构筑块，通过可逆加成-断裂链转移（RAFT）技术。RAFT 试剂通过吉西他滨（Gem）官能化作为抗癌药物，并且 squalenyl-methacrylate（SqMA）的聚合导致具有明确结构的大分子前药，每个聚合物链的末端都有一个 Gem。所得 Gem-PSqMA 缀合物的两亲性质允许它们自组装成长期稳定且分散性窄的纳米粒子，在各种癌细胞系上具有显著的体外抗癌活性。为了赋予这些纳米粒子隐形特性，成功地对其进行了聚乙二醇（PEG）化，这通过 X 射线光电子能谱（XPS）和补体激活测定得到了证实。还表明，与非 PEG 化的纳米粒子相比，PEG 化的纳米粒子可以更大量地被癌细胞内化。
