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

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.

Single-Walled (Magnetic) Carbon Nanotubes in a Pectin Matrix in the Design of an Allantoin Delivery System

“…Aromatic-group molecules can be easily noncovalently bound to CNTs via strong π−π interactions. 19,20 1D functionalized CNTs (f-CNTs) could enhance the binding to a molecule by interacting through several binding sites due to their flexibility. 21 Magnetic carbon nanotubes (mCNTs) have been developed to impart magnetic properties to CNTs.…”

“…Thanks to their large surface area, unique structure, and excellent physical properties, they are among the best nanomaterials for highly effective drug and biomolecule delivery. They can be conjugated noncovalently or covalently with drugs, biomolecules, and nanoparticles. − Also, due to their extremely wide surface area, a variety of molecules can multiconjugate on their sidewalls. Aromatic-group molecules can be easily noncovalently bound to CNTs via strong π–π interactions. , 1D functionalized CNTs (f-CNTs) could enhance the binding to a molecule by interacting through several binding sites due to their flexibility …”

“…This is a serious problem, especially for biomedical applications. There are a few strategies that are useful for solving solubility problems, such as the functionalization of the CNT surface with hydrophilic macromers/polymers by covalent bonds or noncovalent interactions. ,,, Noncovalent methods are preferable to obtain functionalized CNTs in various applications since the structure of carbon nanotubes is impaired after the chemical reaction in covalent modification, so their inherent physical properties are destroyed. , …”

“…There are a few strategies that are useful for solving solubility problems, such as the functionalization of the CNT surface with hydrophilic macromers/polymers by covalent bonds 43 or noncovalent interactions. 19,20,44,45 Noncovalent methods are preferable to obtain functionalized CNTs in various applications since the structure of carbon nanotubes is impaired after the chemical reaction in covalent modification, so their inherent physical properties are destroyed. 46,47 On the other hand, pectin has great potential in multipurpose applications in the food and healthcare industries due to its biocompatibility, antimicrobial, and anti-inflammatory properties.…”

Single-Walled Carbon Nanotubes as Fluorescent Probes for Monitoring the Self-Assembly and Morphology of Peptide/Polymer Hybrid Hydrogels

“…SWCNTs are highly hydrophobic and must be individually suspended in water to reveal their characteristic fluorescence in the NIR spectral region . Several classes of dispersants are reported to suspend SWCNTs in water, e.g., surfactants, , single-stranded DNA, , amphiphilic polymers, − and also proteins, peptoids, and peptides. − Several studies showed that (Fmoc-)­conjugated amino acids and peptides are able to disperse SWCNTs in an aqueous environment, , and molecular dynamics simulation showed the hybridization of amino acid crystals with carbon nanotubes. , Further, SWCNTs have proven high biocompatibility in several in vivo applications, rendering them favorable for usage in implantable hydrogels. − …”