Engineered multifunctional carbon nanotube-doxorubicin conjugates for pH-triggered drug release

Abstract This study introduces a multifunctional nanosystem using multi-walled carbon nanotubes (MWCNTs) engineered for cancer treatment and bioimaging. The MWCNTs were functionalized with ornithine monohydrochloride (Or), a biocompatible polymer (PEG), and a pH-sensitive dye (Nile Blue) to enhance biocompatibility, enable tumor microenvironment-responsive drug release, and facilitate imaging. The nanosystem was achieved through a multi-step covalent functionalization process. MWCNTs were carboxylated with nitric acid, followed by the sequential EDC/NHS-mediated conjugation of ornithine and ethanolamine. The construct was then grafted with a poly(ethylene glycol) bis(carboxymethyl) ether (PEG) shell and Nile blue dye, before an identical second layer of ornithine and PEG was added to increase functionality. Glucosamine was immobilized as a targeting ligand, resulting in a multifunctional nanosystem. Structural and compositional analyses via Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), Fourier-Transform Infrared Spectroscopy (FTIR), and x-ray Photoelectron Spectroscopy (XPS) confirmed successful surface modifications. The system’s ability to load and release doxorubicin (DOX), an anticancer drug, was evaluated under acidic (pH 6.5) and neutral (pH 7.4) conditions. Results demonstrated controlled DOX release of up to 60% in acidic environments, aligning with tumor microenvironment specificity. In vitro cytotoxicity assays on colon cancer (Caco-2) cells revealed improved therapeutic efficacy of DOX-loaded nanosystems compared to free DOX, with reduced nonspecific toxicity and enhanced cancer cell targeting. The integration of Nile Blue further enabled real-time bioimaging capabilities, offering dual functionality for monitoring drug delivery. This multifunctional MWCNT-based nanosystem demonstrates significant promise as a targeted theranostic platform for effective cancer treatment and real-time bioimaging.