Protein Corona Hampers Targeting Potential of Muc1 Aptamer Functionalized Sn-38 Core-Shell Nanoparticles Publisher Pubmed



Varnamkhasti BS^{1, 2} ; Hosseinzadeh H^{1, 3} ; Azhdarzadeh M^{1, 2} ; Vafaei SY^{1, 2} ; Esfandyarimanesh M¹ ; Mirzaie ZH¹ ; Amini M⁴ ; Ostad SN^{1, 5} ; Atyabi F^{1, 2, 3} ; Dinarvand R^{1, 2, 3}
Source: International Journal of Pharmaceutics Published:2015

Abstract

Nanoparticles have been considered to improve delivery and physicochemical characteristics of bioactive agents in recent years. In this study, a core-shell chitosan nanoparticulate system was prepared for the targeted delivery of SN-38. SN-38, an active metabolite of camptothecin, conjugated to hyaluronic acid (HA) was used as the shell of chitosan nanoparticles decorated with MUC1 aptamer. The conjugation was confirmed by UV and 1H NMR techniques. Targeting efficiency was evaluated by confocal microscopy and flow cytometry. It was shown that MUC1 decoration increased the uptake of nanoparticles by HT29 cells, MUC1 positive cell line, while CHO as MUC1 negative cell line showed no enhanced uptake of decorated nanoparticles. Compared to non-targeted nanoparticles, flow cytometric annexin V/PI analyses showed that the nanoparticles exert cytotoxicity through apoptosis. It was, however, shown that protein corona adsorption at the surface of nanoparticles hampered the cytotoxicity of nanoparticles, as there was no difference between the cytotoxicity of targeted and non-targeted nanoparticles, when treated with bovine serum albumin prior to cytotoxicity study. © 2015 Elsevier B.V. All rights reserved.