Systemic delivery of micelles loading with paclitaxel using N-succinyl-palmitoyl-chitosan decorated with cRGDyK peptide to inhibit non-small-cell lung cancer.

Abstract

This study aimed to prepare efficient cRGDyK peptide-decorated micelles for the targeted therapy of non-small-cell lung cancer (NSCLC). An amphiphilic copolymer N-succinyl-palmitoyl-chitosan (SPCS) was synthesized and characterized. cRGDyK peptide is a ligand that can target tumors via specific binding integrin receptor overexpressed on tumor neovascularization and cells. cRGDyK-functionalized SPCS micelles loaded with paclitaxel (PTX/cRGDyK-SPCS) were prepared by film dispersion method and then characterized according to morphology, size, and zeta potential. PTX/cRGDyK-SPCS micelles presented pH-triggered drug release behavior under acidic conditions. The accumulation of micelles detected by laser confocal fluorescence microscopy and flow cytometry showed that cRGDyK-SPCS micelles were easily taken up by A549 cells marked with the luciferase gene (luc-A549). Meanwhile, co-localization of the micelles and lysosomes was recorded dynamically using a live cell station. MTT assays and cell apoptosis studies revealed that cell viability was significantly inhibited by PTX/cRGDyK-SPCS micelles. More importantly, in vivo animal studies showed that cRGDyK-SPCS micelles mainly accumulated in the orthotopic tumor site. PTX/cRGDyK-SPCS micelles exhibited better anti-tumor activity in subcutaneous and orthotopic lung tumors compared with PTX/SPCS micelles and Taxol(®). These results suggested that PTX/cRGDyK-SPCS micelles had better cancer targeting capacity and superior anti-tumor efficacy. Thus, these micelles have great potential as novel carriers in delivering anti-tumor drugs.

• Authors: Zhi-qiang Yuan, Ji-zhao Li, Yang Liu, Wei-liang Chen, Shu-di Yang, Chun-ge Zhang, Wen-jing Zhu, Xiao-feng Zhou, Chun Liu, Xue-nong Zhang
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 492 Issue 1-2 Pg. 141-51 (Aug 15 2015) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 26188316 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Micelles
• Peptides, Cyclic
• cyclo(Arg-Gly-Asp-Tyr-Lys)
• Chitosan
• Paclitaxel

Topics

• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage, chemistry, therapeutic use)
• Apoptosis (drug effects)
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Chitosan (administration & dosage, analogs & derivatives, chemistry, therapeutic use)
• Drug Delivery Systems
• Female
• Humans
• Lung Neoplasms (drug therapy, pathology)
• Mice, Nude
• Micelles
• Microtubules (drug effects)
• Paclitaxel (administration & dosage, chemistry, therapeutic use)
• Peptides, Cyclic (administration & dosage, chemistry, therapeutic use)
• Tumor Burden (drug effects)