A new peptide ligand for colon cancer targeted delivery of micelles.
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 α6β1 overexpressed on colonic cancer cells. The molecular binding affinity assay indicated that TK had a high binding affinity for integrin α6β1. 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.
a College of Pharmacy, Harbin Medical University (Daqing) , Daqing , China .|b Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University , Shanghai , China .
Yachao
Y
Ren
c College of Veterinary Medicine, Jilin University , Changchun , China , and.
Yu
Y
Mu
a College of Pharmacy, Harbin Medical University (Daqing) , Daqing , China .
Yanping
Y
Song
c College of Veterinary Medicine, Jilin University , Changchun , China , and.
Jinxin
J
Xie
a College of Pharmacy, Harbin Medical University (Daqing) , Daqing , China .
Hui
H
Yu
a College of Pharmacy, Harbin Medical University (Daqing) , Daqing , China .
Sainan
S
Gao
a College of Pharmacy, Harbin Medical University (Daqing) , Daqing , China .
Sen
S
Li
a College of Pharmacy, Harbin Medical University (Daqing) , Daqing , China .
Haisheng
H
Peng
d Animal Technology College, Heilongjiang Bayi Agricultural University , Daqing , China.
Yulong
Y
Zhou
b Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University , Shanghai , China .
Weiyue
W
Lu
D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D003374:Coumarins / Q000009:adverse effects* / Q000737:chemistry / Q000494:pharmacology*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D005434:Flow Cytometry; D006801:Humans; D008024:Ligands; D008823:Micelles; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*
D003374:Coumarins; D008024:Ligands; D008823:Micelles; D010455:Peptides; C000614673:coumarin-6H; D004317:Doxorubicin
Colonic drug delivery; DOX; integrin α6β1 receptor; micelles; peptide ligand