Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.
Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China.
Biomaterials. 2014 May;35(14):4357-67. doi: 10.1016/j.biomaterials.2014.01.070. Epub 2014 Feb 24.
The co-delivery of drug and gene has become the primary strategy in cancer and other disease therapy. To co-deliver hydrophobic drug and functional gene efficiently into tumor cells, a star-shaped copolymer (PP-PLLD-Arg) with a photochemical internalization effect consisting of a porphyrin (PP) core and arginine-functionalized poly(L-lysine) dendron (PLLD-Arg) arms has been designed, and used to co-deliver docetaxel (DOC) and MMP-9 shRNA plasmid for nasopharyngeal cancer therapy. It was found that PP-PLLD-Arg/MMP-9 nanocomplex showed the photo-enhanced gene transfection efficiency in vitro, and could mediate a significant reduce of MMP-9 protein expression in HNE-1 cells. For co-delivery analysis, the obtained PP-PLLD-Arg/DOC/MMP-9 complexes could induce a more significant apoptosis than DOC or MMP-9 used only, and decreased invasive capacity of HNE-1 cells. Moreover, the star-shaped copolymer exhibited better blood compatibility and lower cytotoxicity compared to PEI-25k in the hemolysis and MTT assays, and also showed a good biocompatibility in vivo. Therefore, PP-PLLD-Arg with suited irradiation is a promising non-toxic and photo-inducible effective drug and gene delivery strategy, which should be encouraged in tumor therapy.
药物和基因的共递送已成为癌症和其他疾病治疗的主要策略。为了将疏水性药物和功能基因有效地递送到肿瘤细胞中，设计了一种具有光化学内化效应的星形共聚物（PP-PLLD-Arg），由卟啉（PP）核心和精氨酸功能化的聚（L-赖氨酸）树枝状大分子（PLLD-Arg）臂组成，并用于共递送多西紫杉醇（DOC）和 MMP-9 shRNA 质粒进行鼻咽癌治疗。结果表明，PP-PLLD-Arg/MMP-9 纳米复合物在体外具有光增强的基因转染效率，并能介导 HNE-1 细胞中 MMP-9 蛋白表达的显著降低。对于共递药分析，所得的 PP-PLLD-Arg/DOC/MMP-9 复合物比单独使用 DOC 或 MMP-9 能诱导更显著的细胞凋亡，并降低 HNE-1 细胞的侵袭能力。此外，与 25kDa 的 PEI 相比，星形共聚物在溶血和 MTT 测定中表现出更好的血液相容性和更低的细胞毒性，并且在体内也表现出良好的生物相容性。因此，具有合适辐射的 PP-PLLD-Arg 是一种有前途的非毒性和光诱导的有效药物和基因递送策略，应在肿瘤治疗中得到鼓励。
