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: Dong Ma, Qian-Ming Lin, Li-Ming Zhang, Yuan-Yuan Liang, Wei Xue
• Journal: Biomaterials (Biomaterials) Vol. 35 Issue 14 Pg. 4357-67 (May 2014) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 24576804 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Biocompatible Materials
• Porphyrins
• RNA, Messenger
• Taxoids
• Docetaxel
• Polylysine
• Arginine
• Matrix Metalloproteinase 9

Topics

• Animals
• Apoptosis (drug effects)
• Arginine (chemistry)
• Biocompatible Materials (pharmacology)
• Cell Line, Tumor
• Chromatography, Gel
• Docetaxel
• Drug Delivery Systems
• Female
• Flow Cytometry
• Gene Transfer Techniques
• Hemolysis (drug effects)
• Humans
• Light
• Magnetic Resonance Spectroscopy
• Matrix Metalloproteinase 9 (genetics, metabolism)
• Mice
• Particle Size
• Polylysine (chemical synthesis, chemistry)
• Porphyrins (chemical synthesis, chemistry)
• Protein Binding (drug effects)
• RNA, Messenger (genetics, metabolism)
• Static Electricity
• Taxoids (pharmacology)
• Transfection