Noncovalent Pyrene-Polyethylene Glycol Coatings of Carbon Nanotubes Achieve in Vitro Biocompatibility

Abstract

Single-walled carbon nanotubes (SWNTs) have become increasingly exploited in biological applications, such as imaging and drug delivery. The application of SWNTs in biological settings requires the surface chemistry to remain through the low solubility in aqueous media. In this research, a facile approach for the preparation of a polyethylene glycol (PEG)-coated SWNT-based nanocarrier was reported. We focused on the effect of PEG chain length and SWNT size on the cytotoxicity of PEG-coated SWNTs as a superior drug delivery nanovector. First, all-atom molecular dynamics (MD) simulations were employed to explore the stability and behavior of SWNT/pyrene-PEG (SWNT/Pyr-PEG) structures at a molecular level that is not attainable with experiments. The MD studies revealed that (i) π-π stacking interactions between the pyrene bearing PEG molecules and SWNTs are maintained in bulky situations, regardless of PEG molecular weight or SWNT size; (ii) pyrene molecules diffuse over the SWNT surface without detaching; and (iii) both short and long dynamic Pyr-PEG chains have the capability of effectively coating the SWNT surface. In light of the simulations, noncovalent (π-π stacking) assemblies of SWNT/Pyr-PEG with different molecular weights of PEG ( M = 2000, 5000, and 12000) were successfully fabricated and characterized. For longer PEG chains, more effective coating of SWNTs was obtained, resulting in more biocompatible SWNT/Pyr-PEG nanomaterials. The number of SWNTs coated by Pyr-PEG was highly dependent on the length of pyrene bearing PEG polymers. Moreover, the short SWNTs showed a higher amount of PEG coating with respect to the long SWNTs. Cell viability results demonstrated a dose-dependent cytotoxicity of coated SWNTs. Short SWNTs coated with longer PEG chains have low cytotoxicity to be used in in vivo studies.

Molecular dynamics simulations of adsorption of long pyrene-PEG chains on athin carbon nanotube

“…The average interaction energy of the pyrene-PEG 2000 complex to SWNT was calculated as -71.57 kcal/mol and that of pyrene-PEG 5000 was -77.59 kcal/mol in water, which were close to each other. These energy values also agreed with our previous findings [32], which indicated interaction energies of -65.99 kcal/mol for pyrene-PEG 2000 and -72.05 kcal/mol for pyrene-PEG 5000 .…”

Biocompatibility and Carcinogenicity of Carbon Nanotubes as Biomaterials

“…PEGylated SWCNTs showed prolonged blood circulation half-life and stability in serum. In addition, Meran et al [44] evaluated the effects of PEGylated SWCNTs on human umbilical vein endothelial cells (HUVECs). MTT assays were performed using longer SWCNTs with a diameter of 7 Å and length of 120 Å and compared to shorter SWCNTs with a length of 40 Å.…”

Molecular Simulations of PEGylated Biomolecules, Liposomes, and Nanoparticles for Drug Delivery Applications

“…Fullerene molecules were also included to the inner cavity of CNT functionalized with PEG and folic acid, where fullerenes act as magnetic pistons at acidic pH, leading to an increase in the release of doxorubicin from nanotube [217], which helps explain the effect of PEG on the efficiency of drug release as well as suggests the use of fullerene, as presented in Figure 9. Meran et al simulated CNTs coated with PEGylated pyrene and showed the adsorption of PEGylated pyrene onto the CNT surface via π-π stacking interactions, which does not significantly depend on PEG length and CNT size [218]. Saberinasab et al performed quantum-mechanics (QM) calculations and all-atom MD simulations of a mixture of PEGylated CNTs and Temozolomide (anticancer drug), showing the adsorption of Temozolomide on PEGylated CNT because of strong hydrogen-bond interactions [219].…”