Fmoc-PEG Coated Single-Wall Carbon Nanotube Carriers by Non-covalent Functionalization: An Experimental and Molecular Dynamics Study.

Yesim Yeniyurt,Ozge Kurkcuoglu,Nilgun Karatepe,Sila Kilic,Ö Zeynep Güner-Yılmaz,Elif Baysak,Mehdi Meran,Serdar Bozoglu,Gurkan Hizal,Saime Batirel,F Seniha Güner

doi:10.3389/fbioe.2021.648366

Abstract

Due to their structural characteristics at the nanoscale level, single-walled carbon nanotubes (SWNTs), hold great promise for applications in biomedicine such as drug delivery systems. Herein, a novel single-walled carbon nanotube (SWNT)-based drug delivery system was developed by conjugation of various Fmoc-amino acid bearing polyethylene glycol (PEG) chains (Mw = 2,000, 5,000, and 12,000). In the first step, full-atom molecular dynamics simulations (MD) were performed to identify the most suitable Fmoc-amino acid for an effective surface coating of SWNT. Fmoc-glycine, Fmoc-tryptophan, and Fmoc-cysteine were selected to attach to the PEG polymer. Here, Fmoc-cysteine and -tryptophan had better average interaction energies with SWNT with a high number of aromatic groups, while Fmoc-glycine provided a non-aromatic control. In the experimental studies, non-covalent modification of SWNTs was achieved by Fmoc-amino acid-bearing PEG chains. The remarkably high amount of Fmoc-glycine-PEG, Fmoc-tryptophan-PEG, and Fmoc-cysteine-PEG complexes adsorbed onto the SWNT surface, as was assessed via thermogravimetric and UV-vis spectroscopy analyses. Furthermore, Fmoc-cysteine-PEG5000 and Fmoc-cysteine-PEG12000 complexes displayed longer suspension time in deionized water, up to 1 and 5 week, respectively, underlying the ability of these surfactants to effectively disperse SWNTs in an aqueous environment. In vitro cell viability assays on human dermal fibroblast cells also showed the low cytotoxicity of these two samples, even at high concentrations. In conclusion, synthesized nanocarriers have a great potential for drug delivery systems, with high loading capacity, and excellent complex stability in water critical for biocompatibility.

Highlights

Among nanocarriers, single-walled carbon nanotubes (SWNTs) are currently one of the most investigated materials, and a great deal of effort is devoted to expanding their biomedical applications, for treatment (Mehdipoor et al, 2011; Sheikhpour et al, 2017) and imaging (Yudasaka et al, 2017) purposes
Long hydrophilic Fmoc-polyethylene glycol (PEG) chains were conjugated to SWNTs through π-π interactions
We demonstrated the successful synthesis of Fmoc-amino acid-PEG complexes, which were further employed for the surface coating of SWNTs

Summary

INTRODUCTION

Single-walled carbon nanotubes (SWNTs) are currently one of the most investigated materials, and a great deal of effort is devoted to expanding their biomedical applications, for treatment (Mehdipoor et al, 2011; Sheikhpour et al, 2017) and imaging (Yudasaka et al, 2017) purposes. Six different Fmoc-amino acid-coated SWNT complexes were constructed, in which five aromatic amino acids, tryptophan, tyrosine, histidine, phenylalanine, and S-trityl-L-cysteine, and non-aromatic glycine were investigated. This study explains how to functionalize SWNTs with Fmoc-amino acid bearing PEGs. It brings a new perspective to the non-covalent functionalization of SWNTs, using a highly effective biocompatible coating that significantly improves the water suspension time and achieves low cytotoxicity on human fibroblast cells. We investigated six N-(fluorenyl-9-methoxycarbonyl) (Fmoc) attached amino acids, which are glycine (G), phenylalanine (F), histidine (H), tryptophan (W), tyrosine (Y), and S-tritylL-cysteine (C), to understand their extent of interactions with the SWNT surface. The dispersion behavior was monitored for all Fmoc-PEG functionalized SWNTs. In-vitro Cell Viability Assay Cytotoxicity of the samples was evaluated with MTT-assay.

RESULTS AND DISCUSSION

CONCLUSION

DATA AVAILABILITY STATEMENT