S2P peptide-conjugated PLGA-Maleimide-PEG nanoparticles containing Imatinib for targeting drug delivery to atherosclerotic plaques.

BACKGROUND: Imatinib is a platelet-derived growth factor receptor (PDGFR) inhibitor with very low water solubility. Previous studies in atherosclerosis have shown that PDGFR activity has an egregious effect on vascular disease and progression of atherosclerosis. Specific ligands of atherosclerotic plaques can be used for targeting of nanoparticles. Studies in atherosclerosis proved that stabilin-2 is a glycoprotein which exists abundantly in atherosclerotic plaques and it is produced from both macrophages and endothelial cells. OBJECTIVES: The objective of this study is the targeting drug delivery to atherosclerotic plaques by using imatinib-loaded nanoparticles modified by S2P peptide. METHODS: The imatinib-loaded nanoparticles were fabricated through a modified emulsion/solvent evaporation technique. After fabricating PLGA nanoparticles, maleimide PEG was used as linker between PLGA nanoparticles and S2P peptide. Because of presence cysteine in both side of S2P peptide, maleimide formed a thiolether linkage by thiol group of cysteine. Then the physicochemical analysis like H-NMR, FT-IR, DSC, SEM, particle size, zeta potential, and drug release were studied. RESULTS: Stabilin-2 peptide with sequence of CRTLTVRKC is a specific ligand to stabilin-2, so it was synthesized for using as the targeting agent for atherosclerosis. S2P peptide conjugation to the surface of nanoparticles was proved by H-NMR and FT-IR, and the percentage of S2P peptide in nanoparticles was 1.3%. The final nanoparticles were spherical and their size were 183 nm. The loading capacity of the imatinib-loaded nanoparticles was 5.05%. The sustained release profile was observed for peptide targeted nanoparticles. CONCLUSION: The chosen method was simple, reproducible, and specific in peptide conjugation of nanoparticles for targeting delivery to atherosclerotic regions. Graphical abstract .

Specific targeting delivery to MUC1 overexpressing tumors by albumin-chitosan nanoparticles conjugated to DNA aptamer.

Chitosan-coated human serum albumin nanoparticles were functionalized by MUC1 aptamer to obtain a selective drug carrier toward cancers overexpressing MUC1. The negative charges of albumin nanoparticles were shifted to positive charges by surface modification with chitosan, and MUC1 was conjugated through an acrylate spacer. The cytotoxicity of targeted nanoparticles was significantly more than non-aptamer nanoparticles, and also the chitosan-coated nanoparticles had more cytotoxic effects than the negatively charged albumin nanoparticles. The IC50 of targeted nanoparticles was 28 and 26% of free paclitaxel in MCF7 and T47D cells at 48h, respectively. Confocal laser scanning electron microscopy showed that aptamer conjugation and positive charge increase the cellular uptake. 66% of paclitaxel was released within 32h, but 100% of drug was released at pH=5.5 (similar cancer cells). The paclitaxel plasma amount was at a good level of 17.6% at 2h for increasing the chance of cellular uptake.