Targeting peptide iRGD-conjugated amphiphilic chitosan-co-PLA/DPPE drug delivery system for enhanced tumor therapy

In this paper, we report a novel targeting drug delivery system, obtained using an amphiphilic chitosan-co-(D,L-lactide)/1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine copolymer (CS-co-PLA/DPPE) with the modification of an iRGD (CRGDKGPDC) peptide as the targeting module. Hydrophilic doxorubicin (DOX) was encapsulated and cell experiments were carried out to evaluate the anti-tumor efficacy of DOX-loaded nanoparticles (NPs) in vitro. Characterization data showed a favorable size distribution, high encapsulation efficiency and a pH-dependent release profile for the synthesized NPs. A cytotoxicity assay revealed the higher inhibitory effect of DOX–iRGD–NPs especially in cell lines with an abundant expression of αvβ3 integrin receptors. An increased cellular uptake of DOX–iRGD–NPs was observed and further confirmed to be a consequence of a specific endocytosis pathway mediated by ligand–receptor interactions. Visualization of the intracellular trafficking showed different distributions of DOX when delivered using DOX–NPs and DOX–iRGD–NPs, proving the targeting effect of iRGD. With the help of the iRGD targeting peptide, a chemotherapeutic drug can be delivered specifically to the cancer and endothelial cells expressing αvβ3 integrin receptors to achieve an enhanced anti-tumor efficacy and controlled drug release.