title: TNYL peptide functional chitosan-g-stearate conjugate micelles for tumor specific targeting.
abstract: Nowadays, a real challenge in cancer therapy is to design drug delivery systems that can achieve high concentrations of drugs at the target site for improved therapeutic effect with reduced side effects. In this research, we designed and synthesized a homing peptide-(TNYLFSPNGPIA, TNYL) modified chitosan-g-stearate (CS) polymer micelle (named T-CS) for targeting delivery. The peptide displayed specific binding affinity to EphB4 which is a member of the Eph family of receptor tyrosine protein kinases. The amphiphilic polymer T-CS can gather into micelles by themselves in an aqueous environment with a low critical micelle concentration value (91.2 μg/L) and nano-scaled size (82.1 ± 2.8 nm). The drug encapsulation efficiency reached 86.43% after loading the hydrophobic drug doxorubicin (DOX). The cytotoxicity of T-CS/DOX against SKOV3 cells was enhanced by approximately 2.3-fold when compared with CS/DOX. The quantitative and qualitative analysis for cellular uptake indicated that TNYL modification can markedly increase cellular internalization in the EphB4-overexpressing SKOV3 cell line, especially with a short incubation time. It is interesting that relatively higher uptake of the T-CS/DOX micelles by SKOV3 cells (positive-EphB4) than A549 cells (negative-EphB4) was observed when the two cells were co-incubated. Furthermore, in vivo distribution experiment using a bilateral-tumor model showed that there was more fluorescence accumulation in the SKOV3 tumor than in the A549 tumor over the whole experiment. These results suggest that TNYL-modified CS micelles may be promising drug carriers as targeting therapy for the EphB4-overexpressing tumor.
authors.affiliation: Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Feng-Ying
authors.initials: FY
authors.lastname: Chen
authors.affiliation: Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Yan
authors.affiliation: College of Pharmaceutical Science, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Han-Xi
authors.initials: HX
authors.lastname: Yi
authors.affiliation: College of Pharmaceutical Science, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Fu-Qiang
authors.initials: FQ
authors.lastname: Hu
authors.affiliation: College of Pharmaceutical Science, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Yong-Zhong
authors.initials: YZ
authors.lastname: Du
authors.affiliation: College of Pharmaceutical Science, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
authors.affiliation: College of Pharmaceutical Science, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: You
authors.affiliation: Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Meng-Dan
authors.initials: MD
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry* / Q000493:pharmacokinetics; D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D018613:Microscopy, Confocal; D010455:Peptides / Q000737:chemistry* / Q000493:pharmacokinetics; D013229:Stearic Acids / Q000737:chemistry* / Q000493:pharmacokinetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D010455:Peptides; D013229:Stearic Acids; C509441:TNYL-RAW peptide; C031183:stearic acid; D004317:Doxorubicin; D048271:Chitosan
keywords: TNYL; active targeting; antitumor activity; chitosan-g-stearate; polymeric micelles