Microtubule-Inspired Functionalization of Carbon Nanotubes: A Biomimetic Carrier Design

We propose a bioinspired, non-covalent carbon nanotubes (CNTs) functionalization strategy to augment their bioavailability and alleviate their biotoxicity. For functionalization, select amphiphilic peptides from a cytoskeletal biopolymer, microtubule (MT), were used. The peptides are involved in the MT polymerization by maintaining the essential lateral interactions among the MT’s α- and β-tubulin subunits. They also participate in forming the MT-binding sites for hosting several MT-targeting antimitotics. Utilizing in silico methods, this study showed the peptides influenced CNT’s diffusivity and aqueous solubility. The hydrodynamic shield formed by the peptides from β-tubulin was more widespread on the CNT than the α-tubulin peptides’; however, the latter created a broader hydrophobic CNT coating than those from the β-tubulin. In particular, the peptides consisting of the H1-B2, H10, H1-B2, and the M-loop, demonstrated structural features that serve to augment CNTs’ water solubility and dispersibility. The performance of the peptide-functionalized CNTs as drug carriers was examined by studying seventeen antimitotics. The CNT-peptides structural composition was identified as a suitable carrier for phomopsin A, laulimalide, epothilone A, epothilone D, discodermolide, eribulin, and docetaxel. The peptides played dual roles displaying affinities to the antimitotics and the CNT; in particular, the peptides from the H1-B2 and H2-B3 loops of β-tubulin exhibited exceptional binding properties. Specific mutations on the wildtype peptides, including those from the α-tubulin M-loop and H2-B3, or the β-tubulin H1-B2, are proposed to refine their hydrophobicity, eliminate unfavorable inter-peptides electrostatic interactions or the spatial hindrance at certain regions, to enhance their conformational steadiness and exposure to the tube surface. A combination of the select amphiphilic peptides from both tubulin subunits is suggested to improve CNTs bioavailability and efficiency for carrying insoluble hydrophobic cargos.