PEGylated multi-walled carbon nanotubes as versatile vector for tumor-specific intracellular triggered release with enhanced anti-cancer efficiency: Optimization of length and PEGylation degree

Abstract

PEGylated multi-walled carbon nanotubes (PEG-MWCNTs) were optimized as versatile vector for tumor-specific intracellular triggered release of doxorubicin (DOX), based on the effect of their length and PEGylation degree on the cytotoxicity and DOX-loading capacity. The length and surface carboxyl groups of the carboxylated multi-walled carbon nanotubes (CMWCNTs) were easily tailored by adjusting the oxidation time. The longer CMWCNTs or those with high carboxyl group content showed obvious cytotoxicity, while the PEG-MWCNTs ≤ 300 nm showed better cytocompatibility. The PEG-MWCNTs-3 of about 300 nm was selected as drug delivery vector, possessing a high drug-loading capacity of 0.55 mg/mg. They released DOX rapidly under lower pH media mimicking the tumor microenvironment with cumulative release of 57% within 24 h, while the premature leakage under the simulated physiological condition was only 10%. The WST-1 assays demonstrated the DOX-loaded PEG-MWCNTs-3 exhibited the enhanced inhibitory efficiency against HepG2 cells, in comparison with free DOX.

Keywords: Drug delivery system; Length; Multi-walled carbon nanotubes; PEGylation degree; Tumor-specific intracellular triggered release.