title: A star-shaped porphyrin-arginine functionalized poly(L-lysine) copolymer for photo-enhanced drug and gene co-delivery.
abstract: 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.
authors.affiliation: Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Ma
authors.affiliation: Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Qian-Ming
authors.initials: QM
authors.lastname: Lin
authors.affiliation: Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China. Electronic address: ceszhlm@mail.sysu.edu.cn.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Zhang
authors.affiliation: Research Center for Biomedicine and Health, Hangzhou Normal University, Hangzhou 310012, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Liang
authors.affiliation: Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China; Institute of Life and Health Engineering, Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Jinan University, Guangzhou 510632, China. Electronic address: weixue_jnu@aliyun.com.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Xue
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001120:Arginine / Q000737:chemistry*; D001672:Biocompatible Materials / Q000494:pharmacology; D045744:Cell Line, Tumor; D002850:Chromatography, Gel; D000077143:Docetaxel; D016503:Drug Delivery Systems; D005260:Female; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010316:Particle Size; D011107:Polylysine / Q000138:chemical synthesis / Q000737:chemistry*; D011166:Porphyrins / Q000138:chemical synthesis / Q000737:chemistry*; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055672:Static Electricity; D043823:Taxoids / Q000494:pharmacology; D014162:Transfection
chemical_list: D001672:Biocompatible Materials; D011166:Porphyrins; D012333:RNA, Messenger; D043823:Taxoids; D000077143:Docetaxel; D011107:Polylysine; D001120:Arginine; D020780:Matrix Metalloproteinase 9
keywords: Arginine; Co-delivery; Lysine; Photo-enhanced; Porphyrin; Star polymers