title: pH responsive micelle self-assembled from a new amphiphilic peptide as anti-tumor drug carrier.
abstract: An acid-responsive amphiphilic peptide that contains KKGRGDS sequence in hydrophilic head and VVVVVV sequence in hydrophobic tail was designed and prepared. In neutral or basic medium, this amphiphilic peptide can self-assemble into micelles through hydrogen bonding and hydrophobic interactions. If changing the solution pH to an acidic environment, the electrostatic repulsion interaction among the ionized lysine (K) residues will prevent the self-assembly of the amphiphilic peptide, leading to the dissociation of micelles. The anti-tumor drug of doxorubicin (DOX) was chosen and loaded into the self-assembled micelles of the amphiphilic peptide to investigate the influence of external pH change on the drug release behavior. As expected, the micelles show a sustained DOX release in neutral medium (pH 7.0) but fast release behavior in acidic medium (pH 5.0). When incubating these DOX-loaded micelles with HeLa and COS7 cells, due to the over-expression of integrins on cancer cells, the micelles can efficiently use the tumor-targeting function of RGD sequence to deliver the drug into HeLa cells. Combined with the low cytotoxicity of the amphiphilic peptide against both HeLa and COS7 cells, the amphiphilic peptide reported in this work may be promising in clinical application for targeted drug delivery.
authors.affiliation: Chemical Engineering and Pharmaceutics School, Henan University of Science and Technology, Luoyang 471023, PR China; Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan 430072, PR China.
authors.forename: Ju
authors.initials: J
authors.lastname: Liang
authors.affiliation: Medical School, Henan University of Science and Technology, Luoyang 471003, PR China.
authors.forename: Wen-Lan
authors.initials: WL
authors.lastname: Wu
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan 430072, PR China. Electronic address: xd-xu@whu.edu.cn.
authors.forename: Xiao-Ding
authors.initials: XD
authors.lastname: Xu
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan 430072, PR China.
authors.forename: Ren-Xi
authors.initials: RX
authors.lastname: Zhuo
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan 430072, PR China. Electronic address: xz-zhang@whu.edu.cn.
authors.forename: Xian-Zheng
authors.initials: XZ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D004317:Doxorubicin / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D042541:Intracellular Space / Q000378:metabolism; D008823:Micelles; D010316:Particle Size; D010455:Peptides / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D010455:Peptides; D013501:Surface-Active Agents; D004317:Doxorubicin
keywords: Amphiphilic peptide; Drug carrier; Self-assembly; Tumor-targeting; pH responsive