a Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry , Wuhan University , Wuhan , China.
b Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan / School of Chemistry and Chemical Engineering , Shihezi University , Shihezi , China.
J Biomater Sci Polym Ed. 2018 Jan;29(1):92-106. doi: 10.1080/09205063.2017.1400146. Epub 2017 Nov 8.
In this paper, novel folate-conjugated and redox-responsive crosslinked block copolymer was successfully synthesized for targeted and controlled release of doxorubicin (DOX) to cancer cells. Folate-conjugated poly(ethylene glycol)-b-copolycarbonates (FA-PEG-b-P(MAC-co-DTC)) and methoxy poly(ethylene glycol)-b-copolycarbonates (mPEG-b-P(MAC-co-DTC)) were firstly synthesized by enzymatic method. FA-PEG/mPEG-b-P(MAC-co-DTC)-SS was then obtained by further crosslinking reaction with cystamine. Non-conjugated crosslinked copolymer mPEG-b-P(MAC-co-DTC)-SS- and non-conjugated uncrosslinked copolymer mPEG-b-P(MAC-co-DTC) were also synthesized for comparison. All the amphiphlic copolymers could self-assemble to form nano-sized micelles which dispersed in spherical shape before and after DOX loading. The core crosslinking structure of FA-PEG/mPEG-b-P(MAC-co-DTC)-SS could improve the micellar stability and drug loading capacity, while in vitro release studies also showed more sustained drug release behavior which could be accelerated in reductive condition. Moreover, confocal laser scanning microscopy indicated that the conjugation of FA could enhance the cellular uptake efficiency obviously via FA-receptor-mediated endocytosis, and MTT assays demonstrated highly potent cytotoxic activity of FA-PEG/mPEG-b-P(MAC-co-DTC)-SS.
在本文中，成功合成了一种新型的叶酸偶联和氧化还原响应的交联嵌段共聚物，用于阿霉素（DOX）向癌细胞的靶向和控制释放。叶酸偶联的聚乙二醇-b-共碳酸酯（FA-PEG-b-P（MAC-co-DTC））和甲氧基聚乙二醇-b-共碳酸酯（mPEG-b-P（MAC-co-DTC））首先通过酶法合成。然后通过与胱胺的进一步交联反应得到 FA-PEG/mPEG-b-P（MAC-co-DTC）-SS。还合成了非偶联交联共聚物 mPEG-b-P（MAC-co-DTC）-SS-和非偶联未交联共聚物 mPEG-b-P（MAC-co-DTC）进行比较。所有两亲嵌段共聚物都可以自组装形成纳米级胶束，在负载 DOX 前后分散成球形。FA-PEG/mPEG-b-P（MAC-co-DTC）-SS 的核交联结构可以提高胶束的稳定性和载药能力，而体外释放研究也表明在还原条件下可以加速更持续的药物释放行为。此外，共聚焦激光扫描显微镜表明，FA 的偶联可以通过 FA-受体介导的内吞作用明显增强细胞摄取效率，MTT 测定表明 FA-PEG/mPEG-b-P（MAC-co-DTC）-SS 具有很高的细胞毒性活性。
