A comparative study on penetration mechanisms of drug-loaded carbon and boron nitride nanotubes through biological membranes by steered molecular dynamics simulations

Abstract

Understanding the mechanism by which nanotubes penetrate cell membranes is challenging from multiple perspectives. As a drug delivery system, boron nitride nanotubes (BNNTs) have a similar structure to carbon nanotubes but with B–N bonds instead of C–C bonds. Through a remarkable series of direct and indirect observations within specific cells, these nanotubes are popularly attributed as superior penetrant into cell membrane. Suitable functional groups and polymers are often needed to enhance the biocompatibility and solubility of BNNTs and CNTs in biological media. In addition, to figure out the effect of functional groups, the nanostructures without functional groups were first examined together with their anticancer drugs (fluorouracil and letrozole). All partial charges of the drug and nanotube have been investigated through population analysis. After that, with a total of 40 simulations (MD and SMD simulations), various analytical techniques were employed to examine the interaction between drugs and nanotubes with POPE, which is a class of phospholipids existing in biological membrane, in aqueous media. Noteworthy among these techniques is the mean-squared displacement analysis to compare the diffusion rate of nanocarriers and the radial distribution function analysis, which was utilized to compare water concentrations surrounding nanotubes. Additionally, the stability of the drug within the nanotube was assessed through mass center distance analysis. The diffusion coefficients of the nanotube-membrane complex were compared against various chemical agents by employing mean squared displacement analysis. The findings of the study revealed that the tethering of tetra ethylene glycol results in the augmentation of the water molecules surrounding the nanotubes while simultaneously enhancing the durability of the drug being conveyed. Nonetheless, the addition of tetra ethylene glycol resulted in a reduction in the nanocarrier’s diffusion coefficient. Communicated by Ramaswamy H. Sarma