Self-aggregated pegylated poly (trimethylene carbonate) nanoparticles decorated with c(RGDyK) peptide for targeted paclitaxel delivery to integrin-rich tumors.

Abstract

Cyclic RGD peptide-decorated polymeric micellar-like nanoparticles (MNP) based on PEGylated poly (trimethylene carbonate) (PEG-PTMC) were prepared for active targeting to integrin-rich cancer cells. An amphiphilic diblock copolymer, α-carboxyl poly (ethylene glycol)-poly (trimethylene carbonate) (HOOC-PEG-PTMC), was synthesized by ring-opening polymerization. The c(RGDyK) ligand, a cyclic RGD peptide that can bind to the integrin proteins predominantly expressed on the surface of tumor cells with high affinity and specificity, was conjugated to the NHS-Activated PEG terminus of the copolymer. The c(RGDyK)-functionalized PEG-PTMC micellar nanoparticles encapsulating PTX (c(RGDyK)-MNP/PTX) was fabricated by the emulsion/solvent evaporation technique and characterized in terms of morphology, size and zeta potential. Cellular uptake of c(RGDyK)-MNP/PTX was found to be higher than that of MNP/PTX due to the integrin protein-mediated endocytosis effect. In vitro cytotoxicity, cell apoptosis and cell cycle arrest studies also revealed that c(RGDyK)-MNP/PTX was more potent than those of MNP/PTX and Taxol. Pharmacokinetic study in rats demonstrated that the polymeric micellar nanoparticles significantly enhanced the bioavailability of PTX than Taxol. In vivo multispectral fluorescent imaging indicated that c(RGDyK)-MNP/PTX had high specificity and efficiency in tumor active targeting. Therefore, the results demonstrated that c(RGDyK)-decorated PEG-PTMC MNP developed in this study could be a potential vehicle for delivering hydrophobic chemotherapeutic agents to integrin-rich tumors.

• Authors: Xinyi Jiang, Xianyi Sha, Hongliang Xin, Liangcen Chen, Xihui Gao, Xiao Wang, Kitki Law, Jijin Gu, Yanzuo Chen, Ye Jiang, Xiaoqing Ren, Qiuyue Ren, Xiaoling Fang
• Journal: Biomaterials (Biomaterials) Vol. 32 Issue 35 Pg. 9457-69 (Dec 2011) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 21911250 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Coumarins
• Dioxanes
• Integrins
• Peptides
• Polymers
• Thiazoles
• coumarin 6
• polytrimethylene carbonate
• Polyethylene Glycols
• Paclitaxel

Topics

• Amino Acid Sequence
• Animals
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Coumarins (metabolism)
• Dioxanes (chemical synthesis, chemistry)
• Drug Delivery Systems (methods)
• Humans
• Integrins (metabolism)
• Magnetic Resonance Spectroscopy
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Molecular Sequence Data
• Nanoparticles (chemistry, ultrastructure)
• Neoplasms (drug therapy, pathology)
• Paclitaxel (pharmacokinetics, pharmacology, therapeutic use)
• Particle Size
• Peptides (chemistry)
• Polyethylene Glycols (chemical synthesis, chemistry)
• Polymers (chemical synthesis, chemistry)
• Rats
• Rats, Sprague-Dawley
• Spectroscopy, Fourier Transform Infrared
• Subcellular Fractions (drug effects, metabolism)
• Thiazoles (metabolism)