Mitoxantrone release from Fmoc-protected amino acids coated magnetic carbon nanotubes: Computational and experimental study for cancer treatment

Nanoparticles have a high potential for use as drug carrier systems in cancer treatment to reduce severe side effects, as in the treatment of many other diseases. Due to their unique properties, carbon-based nanoparticles such as carbon nanotubes (CNTs) are among the most frequently used nanoparticles in drug carrier systems. In this study, magnetic single-walled CNTs (mCNTs) were synthesized, characterized, coated and their ability to carry the anticancer drug mitoxantrone (MTO) was investigated using computational and experimental methods. First, the mCNT coating capabilities of Fmoc-protected amino acids, Fmoc-Cys(trt)-OH and Fmoc-Trp-OH were demonstrated by Raman spectroscopy, thermogravimetric analysis, and X-ray photoelectron spectroscopy. Then, full-atom molecular dynamics simulations of MTO-CNT complexes in explicit water were used to understand Fmoc-amino acid and MTO loading experiments at the molecular level. Binding free energies calculated by the Molecular Mechanics/Poisson-Boltzmann Surface Area method suggested MTO-CNT complex stability even at elevated temperatures up to 350 K that can be achieved due to external magnetic stimuli. Drug loading at pH 9 and releases at physiological (pH 7.4) and lysosomal pH (pH 5.5) were carried out for uncoated and coated mCNTs. The drug release and characterization results showed that coated mCNTs have pH-responsive drug release, enhanced dispersibility, and superparamagnetic properties so they promise to be beneficial for MTO delivery in cancer treatment. Cell viability results demonstrated that the mCNT-Fmoc-Cys samples had higher cell viability compared to the mCNT and mCNT-Fmoc-Trp groups.