Multifunctional modified carbon nanotubes as potential anti-tumor drug delivery

Abstract

The main issues associated with antitumor chemotherapy are the nonspecific and systemic toxicity induced by different types of drugs. In the other hand, the ability of tumor cells to hinder the internalization and metabolism of chemotherapy drugs affects the efficacy of antitumoral therapies. In this context, our work hypothesizes that the development of novel drug delivery systems targeting alternative sites could serve as a strategy to deliver specific and effective antitumoral activity. This study focuses on the synthesis, chemical characterization and biological evaluation of a novel rational dual drug delivery system (DDS) based on non-covalent functionalization. The DDS employed multi-walled carbon nanotubes (MWCNT) as vectors, which are conjugated with folic acid (FA) to facilitate targeted delivery to tumor sites and enhance bioavailability. Additionally, digoxin (DGX) was incorporated as a cytotoxic agent. Several characterization techniques such as X-ray diffraction, thermogravimetric analysis, Raman and infrared spectroscopy were employed to identify the characteristics attributed to the carbon-based nanomaterials and the organic molecules attached on the MWCNT. Transmission electron microscopy analysis revealed the presence of adsorbed aggregates on the surface of the nanotubes. In silico molecular docking studies identified energetically favorable interaction modes between FA and DGX on the MWCNT walls. A drug release assay was performed to elucidate the mechanism of action of the dual drug delivery system. Subsequently, MWCNT, digoxin and the newly developed hybrids were incubated with HeLa cells (cervical cancer) to assess cell viability using the MTT reduction assay. Our findings demonstrated the absence of acute cytotoxicity associated with MWCNT, whereas the DDS exhibited significant cytotoxicity, reducing tumor cell viability at safe concentrations of digoxin. These results shed light on the design and advantages of novel rational drug delivery systems that explore the potential of MWCNT, repurposed antitumor drugs, and membrane tumor biomarkers. Importantly, the synthesis of a dual drug delivery system comprising digoxin and folic acid represents a pioneering achievement in the field to date.