Sustained Release of Mitomycin C from Its Conjugate with Single-Walled Carbon Nanotubes Associated by Pegylated Peptide

A novel sustained release formulation of mitomycin C (MMC) was developed by employing single-walled carbon nanotubes (SWCNTs) wrapped by designed peptide with polyethylene glycol (PEG) modification (pegylation) as a nano-scale molecular platform. The amino groups of polycationic and amphiphilic H-(-Cys-Trp-Lys-Gly-)(-Lys-Trp-Lys-Gly-)₆-OH [CWKG(KWKG)₆] peptide associated with SWCNTs were modified using PEG with 12 units (PEG₁₂) to improve the dispersion stability of the composite. Then thiol groups of peptide were conjugated with MMC using N-ε-maleimidocaproic acid (EMCA) as a linker via transformation of aziridine group of MMC. The obtained SWCNTs-CWKG(KWKG)₆-(PEG)₁₂-C₆-MMC composites particularly that with 13.6% PEG modification extent of amino groups, showed good dispersion stability both in water and in a cell culture medium for 24 h. The release of MMC from SWCNTs-CWKG(KWKG)₆-(PEG)₁₂-C₆-MMC was confirmed to follow first-order kinetics being accelerated by the pH increase in good agreement with the results observed for MMC-dextran conjugate with the same conjugation structure. The SWCNTs-CWKG(KWKG)₆-(PEG)₁₂ composite exhibited a considerably low cytotoxicity against cultured human lung adenocarcinoma epithelial cell line (A₅₄₉). In contrast, SWCNTs-CWKG(KWKG)₆-(PEG)₁₂-C₆-MMC demonstrated delayed but relatively corresponding antitumor activity with free MMC at the same concentration. The results suggested the potential role of SWCNTs-CWKG(KWKG)₆-(PEG)₁₂ as a carrier for a controlled release drug delivery system (DDS).