A star-shaped porphyrin-arginine functionalized poly(l-lysine) copolymer for photo-enhanced drug and gene co-delivery

• Published in: Biomaterials Vol. 35; no. 14; pp. 4357 - 4367
• Main Authors: Ma, Dong, Lin, Qian-Ming, Zhang, Li-Ming, Liang, Yuan-Yuan, Xue, Wei
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.05.2014
• Subjects: Advanced Basic Science; Animals; apoptosis; Apoptosis - drug effects; Arginine; Arginine - chemistry; biocompatibility; Biocompatible Materials - pharmacology; Cell Line, Tumor; Chromatography, Gel; Co-delivery; composite polymers; cytotoxicity; Dentistry; Drug Delivery Systems; drugs; Female; Flow Cytometry; Gene Transfer Techniques; genes; hemolysis; Hemolysis - drug effects; Humans; hydrophobicity; irradiation; Light; Lysine; Magnetic Resonance Spectroscopy; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Mice; neoplasm cells; neoplasms; Particle Size; Photo-enhanced; photochemistry; plasmids; Polylysine - chemical synthesis; Polylysine - chemistry; Porphyrin; porphyrins; Porphyrins - chemical synthesis; Porphyrins - chemistry; Protein Binding - drug effects; protein synthesis; RNA, Messenger - genetics; RNA, Messenger - metabolism; Star polymers; Static Electricity; Taxoids - pharmacology; therapeutics; Transfection; Star polymers; Co-delivery; Arginine; Lysine; Porphyrin; Photo-enhanced
• ISSN: 0142-9612; 1878-5905; 1878-5905
• DOI: 10.1016/j.biomaterials.2014.01.070

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.