title: Construction of surfactant-like tetra-tail amphiphilic peptide with RGD ligand for encapsulation of porphyrin for photodynamic therapy.
abstract: A surfactant-like tetra-tail amphiphilic peptide, [(C(18))(2)K](2)KR(8)GRGDS was designed and synthesized for targeted drug delivery. The resulting peptide-amphiphile, consisting of four hydrophobic aliphatic tails and a hydrophilic peptide head group, was able to self-assemble into nanosized micelles in aqueous medium at low concentration. Ibuprofen and doxorubicin (DOX) was loaded into peptide micelles as model hydrophobic drugs respectively, and the sustained release behavior was observed. Due to the incorporation of targeted arginine-glycine-aspartic acid (RGD) sequences and cell penetrating peptide (CPP) residue octaarginine (R(8)), the micelles could be recognized specifically by cancer cells, as well as transport through the cell membrane efficiently. The observation of laser-scanning confocal microscopy confirmed effective cellular uptaking of porphyrin-loaded peptide micelles. Furthermore, the porphyrin-loaded micelles exhibited low dark toxicity and high phototoxicity against cancer cells, indicating the powerful potential for effective photodynamic therapy. Combined with the low cytotoxicity of the peptide against both HeLa and 293T cell lines, the surfactant-like peptide developed in this study may be promising in clinical application for targeted drug delivery.
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, China.
authors.forename: Jing-Xiao
authors.initials: JX
authors.lastname: Chen
authors.forename: Hui-Yuan
authors.initials: HY
authors.lastname: Wang
authors.forename: Cao
authors.initials: C
authors.lastname: Li
authors.forename: Kai
authors.initials: K
authors.lastname: Han
authors.forename: Xian-Zheng
authors.initials: XZ
authors.lastname: Zhang
authors.forename: Ren-Xi
authors.initials: RX
authors.lastname: Zhuo
mesh_terms: D002460:Cell Line; D057846:Cell-Penetrating Peptides / Q000737:chemistry; D004317:Doxorubicin / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D007052:Ibuprofen / Q000737:chemistry; D008823:Micelles; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D010778:Photochemotherapy / Q000379:methods*; D011166:Porphyrins / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D057846:Cell-Penetrating Peptides; D008823:Micelles; D009842:Oligopeptides; D010455:Peptides; D011166:Porphyrins; D013501:Surface-Active Agents; C448619:octaarginine; C047981:arginyl-glycyl-aspartic acid; D004317:Doxorubicin; D007052:Ibuprofen