A new peptide ligand for colon cancer targeted delivery of micelles. (12th June 2016)

• Record Type: Journal Article
• Authors: Ren, Yachao; Mu, Yu; Song, Yanping; Xie, Jinxin; Yu, Hui; Gao, Sainan; Li, Sen; Peng, Haisheng; Zhou, Yulong; Lu, Weiyue
• Is Part Of: Drug delivery. Volume 23:Number 5(2016:Jul.)
• Page Start: 1763
• Page End: 1772
• Publication Date: 2016-06-12
• Subjects: Colonic drug delivery -- DOX -- integrin α6β1 receptor -- micelles -- peptide ligand; Drug delivery systems -- Periodicals; Drug targeting -- Periodicals; 615.05
• DOI: 10.3109/10717544.2015.1077293
• Languages: English
• ISSNs: 1071-7544

Abstract

Abstract: Ligands are an imperative part of targeted drug delivery systems, and choosing a ligand with high affinity is a subject of considerable interest. In this study, we first synthesized a 12-residue peptide (TK) that interacts with integrin α6 β1 overexpressed on colonic cancer cells. The molecular binding affinity assay indicated that TK had a high binding affinity for integrin α6 β1 . The results of cellular and tumor spheroid uptake suggested that TK peptide not only increases Caco-2 cells uptake, but also effectively increases penetration of the tumor spheroids. TK-conjugated PEG-PLA was synthesized to prepare a novel PEG-PLA micelles loading DOX or coumarin-6 (TK-MS/DOX or TK-MS/C6). The obtained TK-MS/DOX exhibited uniform, spherical shape with a size of 23.80 ± 0.32 nm and zeta potential of 12.21 ± 0.31 mV. The release behavior of DOX from micelles were observed no significant changes after TK modification, however, the release profile exhibited pH-sensitive properties. Compared with MS/DOX, TK-MS/DOX exhibited significantly stronger cytotoxicity for Caco-2. Confocal laser microscopy and flow cytometry data further indicated that the targeting micelles not only had higher uptake by Caco-2 cells, but also more effectively penetrated the tumor spheroids. Therefore, TK peptide appears to be suitable as a targeting ligand with potential applications in colonic targeted therapy.