Short Antiangiogenic MMP-2 Peptide-Decorated Conjugated Linoleic Acid-Coated SPIONs for Targeted Paclitaxel Delivery in an A549 Cell Xenograft Mouse Tumor Model.

ABSTRACT

The design of targeted antiangiogenic nanovectors for the delivery of anticancer drugs presents a viable approach for effective management of nonsmall-cell lung carcinoma (NSCLC). Herein, we report on the fabrication of a targeted delivery nanosystem for paclitaxel (PTX) functionalized with a short antimatrix metalloproteinase 2 (MMP-2) CTT peptide for selective MMP-2 targeting and effective antitumor activity in NSCLC. The fabrication of the targeted nanosystem (CLA-coated PTX-SPIONs@CTT) involved coating of superparamagnetic iron-oxide nanoparticles (SPIONs) with conjugated linoleic acid (CLA) via chemisorption, onto which PTX was adsorbed, and subsequent surface functionalization with carboxylic acid groups for conjugation of the CTT peptide. CLA-coated PTX SPIONs@CTT had a mean particle size of 99.4 nm and a PTX loading efficiency of ∼98.5%. The nanosystem exhibited a site-specific in vitro PTX release and a marked antiproliferative action on lung adenocarcinoma cells. The CTT-functionalized nanosystem significantly inhibited MMP-2 secretion by almost 70% from endothelial cells, indicating specific anti-MMP-2 activity. Treatment of tumor-bearing mice with subcutaneous injection of the CTT-functionalized nanosystem resulted in 69.7% tumor inhibition rate, and the administration of the nanosystem subcutaneously prolonged the half-life of PTX and circulation time in vivo. As such, CLA-coated PTX-SPIONs@CTT presents with potential for application as a targeted nanomedicine in NSCLC management.