Yan Guoqing, Zhang Panpan, Wang Jun, Wang Xin, Tang Rupei
Engineering Research Center for Biomedical Materials, School of Life Science, Anhui University, Hefei 230601, China.
Asian J Pharm Sci. 2020 Nov;15(6):728-738. doi: 10.1016/j.ajps.2019.11.005. Epub 2020 Jan 3.
Although surface PEGylation of nanomedicines can decrease serum protein adsorption , it also blocks uptake by tumor cells. This dilemma could be overcome by employing detachably PEGylated strategy at tumoral extracellular microenvironment to achieve improved cellular uptake while prolonged circulation times. Herein, the amphiphilic graft copolymers with pH-sensitive ortho ester-linked mPEG in side chains and polyurethanes in backbone, can self-assemble into the free and doxorubicin (DOX)-loaded micelles. The pH-sensitive micelles could undergo several characteristics as follows: (i) PEGylated shells for stability in sodium dodecyl sulfonate (SDS) solution; (ii) DePEGylation via degradation of ortho ester linkages at tumoral extracellular pH (6.5) for gradually dynamic size changes and effective release of DOX; and (iii) enhanced cellular uptake and cytotoxicity via positive DOX. Moreover, the dynamic micelles with detachable PEGylation could quickly penetrate the centers of SH-SY5Y multicellular spheroids (MCs) and strongly inhibit tumor growth and , and might be considered as promising and effective drug carriers in tumor therapy.
尽管纳米药物的表面聚乙二醇化可以减少血清蛋白吸附，但它也会阻碍肿瘤细胞的摄取。通过在肿瘤细胞外微环境中采用可分离的聚乙二醇化策略，可以克服这一困境，在延长循环时间的同时提高细胞摄取率。在此，两亲性接枝共聚物的侧链带有pH敏感的原酸酯连接的甲氧基聚乙二醇（mPEG），主链为聚氨酯，可自组装成游离的和负载阿霉素（DOX）的胶束。pH敏感胶束具有以下几个特性：（i）聚乙二醇化外壳在十二烷基磺酸钠（SDS）溶液中保持稳定性；（ii）在肿瘤细胞外pH值（6.5）下通过原酸酯键的降解实现去聚乙二醇化，从而使粒径逐渐动态变化并有效释放DOX；（iii）通过带正电荷的DOX增强细胞摄取和细胞毒性。此外，具有可分离聚乙二醇化的动态胶束可以快速穿透SH-SY5Y多细胞球体（MCs）的中心并强烈抑制肿瘤生长，有望成为肿瘤治疗中有前景的有效药物载体。
