Potential of mZD7349-conjugated PLGA nanoparticles for selective targeting of vascular cell-adhesion molecule-1 in inflamed endothelium.
Early diagnosis and restoring normal function of dysfunctional endothelium is an attractive strategy for prevention of inflammatory diseases such as atherosclerosis. Inhibition of cell adhesion in the process of atherosclerosis plaque formation, mediated by peptide antagonists of very late antigen-4 (VLA-4) has already been developed and evaluated both in vitro and in vivo. In this study, for the first time, modified ZD7349 (mZD7349) peptide, as an antagonist for VLA-4, was used for targeting fluorescein isothiocyanate-loaded poly (DL-lactic-co-glycolic acid) nanoparticles (FITC-PLGA NPs). Rate of binding and internalization of mZD7349-NPs to activated human umbilical vein endothelial cells (HUVECs) were compared with that of untargeted. Effects of temperature reduction and clathrin-mediated endocytosis inhibitor (0.45M sucrose) were also studied on the binding and internalization of mZD7349-NPs and NPs. Results showed that binding of the conjugated NPs could be significantly blocked by pre-incubating cells with the free peptide, suggesting that the binding of NPs is mediated by attaching the surface peptide to VCAM-1 on HUVECs. Also, conjugated FITC-loaded NPs were shown to be rapidly endocytosized to a greater extent than the unconjugated ones. The binding and internalization of mZD7349-NPs and NPs were slowed down at low temperature and in the presence of sucrose with greater reductions for mZD7349-NPs. To conclude, the peptide-NPs targeting the VCAM-1 is suggested as a theranostic carrier for lesions upregulating VCAM-1.
Department of Medical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Fatemeh
F
Imanparast
Department of Medical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Maliheh
M
Paknejad
Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and Biotechnology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Mohammad Ali
MA
Faramarzi
Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Farzad
F
Kobarfard
Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Medical Biomaterials Research Center (MBRC), Tehran University of Medical Sciences, Tehran, Iran. Electronic address: aamani@sina.tums.ac.ir.
Amir
A
Amani
Department of Medical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: Doostimd@sina.tums.ac.ir.
Mahmood
M
Doosti
D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive; D004337:Drug Carriers; D004339:Drug Compounding; D004705:Endocytosis; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry*; D008856:Microscopy, Fluorescence; D058990:Molecular Targeted Therapy; D053758:Nanoparticles; D010456:Peptides, Cyclic / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011485:Protein Binding; D013395:Sucrose / Q000494:pharmacology; D013696:Temperature; D000068936:Theranostic Nanomedicine; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D039041:Integrin alpha4beta1; D010456:Peptides, Cyclic; D019010:Vascular Cell Adhesion Molecule-1; C418806:ZD7349; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D013395:Sucrose
Endothelial cells; PLGA nanoparticles; Vascular cell-adhesion molecule-1; mZD7349 peptide