Transferrin-Mediated Glioblastoma Cell Targeting of Hexagonal Boron Nitrides
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Transferrin-Mediated Glioblastoma Cell Targeting of Hexagonal Boron Nitrides Melis Emanet 1 & Özlem Şen 1 & Mustafa Çulha 1 Received: 12 December 2019 / Accepted: 27 May 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Hexagonal boron nitrides (hBNs) are promising nanomaterials with their high boron content, non-toxic nature in inactive form, high chemical stability, and mechanical strength. However, their hydrophobic nature limits their use in biomedical applications. Therefore, the hBNs have been functionalized with DSPE-PEG-NH2 to increase their colloidal stability and circulation time in bloodstream as well as to provide active sites on their surface for further functionalization with tumor-targeting agents. Then, further functionalization of the DSPE-PEG-hBNs with transferrin (TfR) was applied for selective targeting of transferrin receptors overexpressed by brain tumor cells. After that, the cellular interaction and biocompatibility of the structure was investigated on glioblastoma multiforme (U87MG) cancer cells. The cellular investigations showed that transferrin functionalization of the DSPE-PEG-hBNs increased their uptake by glioblastoma cancer cells and decreased cell viability due to the enhanced cellular internalization. Based on the data, the TfR-DSPE-PEG-hBNs are promising agents to evaluate them in drug carrying and targeting applications. Keywords Hexagonal boron nitride . DSPE-PEG-NH2 . Transferrin . Drug delivery . Cytotoxicity
Introduction In recent years, engineered nanoparticles have gained significant interest in diagnosis and treatment of diseases. Functionalization of the nanoparticles using drug and targeting agents not only increases their cellular internalization capacity but also regulates the intracellular fate of the structures [1–3]. Therefore, a large number of varied biological compounds including proteins, polymers, carbohydrates, phospholipids, and liposomes under investigation for their effects on nanoparticle delivery to the desired cells and tissues depend on the aim of the study [4]. As a commonly used polymeric surface modifier, poly(ethylene glycol) (PEG) provides prolonged circulation of nanoparticles in circulatory system by preventing recognition by mononuclear phagocytic cells as a foreign structure and also increases the endosomal, cytosolic, and nuclear intracellular accumulation [5]. Besides, Melis Emanet and Özlem Şen contributed equally to this work. * Mustafa Çulha [email protected] 1
Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, Ataşehir, 34755 Istanbul, Turkey
entrapment of nanoparticles with liposomes or functionalization with phospholipids in nanosized forms has advantages of being small, flexible, and biocompatible structures that are able to pass through the vein endothelial cells without causing any clots [6]. Owing to the different physicochemical characteristic behaviors of nanosized particles from their micro-sized counterparts, they have changed body distribution performa
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