Development and evaluation of folic acid conjugated curcumin-loaded functionalized multiwalled carbon nanotubes for enhanced efficacy in ovarian cancer treatment

Abstract

The objective of the present study was to enhance the efficacy of curcumin (CUR) by designing a carboxylated multiwalled carbon nanotubes (MWCNT-COOH) based delivery system. In this study, we coupled MWCNT-COOH with folic acid (FA) to create a unique active targeting as well as a pH-responsive formulation for administering CUR to ovarian tumor locations. CUR was loaded onto MWCNT-COOH using the direct method, and then FA conjugation was performed. Using different techniques, such as Fourier transform infrared (FTIR) spectroscopy, Field emission scanning electron microscopy (FE-SEM), Differential light scattering (DLS), Proton Nuclear Magnetic Resonance (¹HNMR) spectroscopy, Raman spectroscopy, X-Ray diffraction (XRD), the curcumin-loaded MWCNTs (CUR-MWCNT-COOH) and the FA-bound formulation (CUR-MWCNT-COOH-FA) were analyzed. The pH-responsive release of CUR-MWCNT-COOH-FA nanocomplexes was observed in a neutral and acidic environment (pH 7.4; pH 4). When comparing pH 4 to pH 7.4, a noticeably higher cumulative percentage of drug release was observed. A dispersion study revealed the presence of functional groups on the outermost surface of both the functionalized MWCNT as well as formulations increased their resilience via converting the hydrophobic MWCNT surface to hydrophilic property. Both CUR-MWCNT-COOH as well as CUR-MWCNT-COOH-FA exhibited a dose-dependent correlation with CUR concentration when it came to in vitro cytotoxicity (measured by SRB assay). SK-OV-3 cell line was used to exhibit significant growth suppression activity against cancer cells at a CUR dose of 40 µg/mL. In conclusion, the addition of FA to CUR-MWCNT-COOH improved the drug's cytotoxicity and cellular absorption along with its bioavailability. Overall, these findings highlight the potential of CUR-MWCNT-COOH-FA as an effective drug-conjugated system for the delivery of CUR to treat ovarian cancer (OC). This study significantly enhances targeted drug delivery techniques for OC by demonstrating the possibility of a novel, pH-responsive, MWCNT-COOH-FA-directed delivery system. Our findings notably show that the addition of FA improves the cellular absorption and bioavailability of CUR-loaded MWCNT-COOH, leading to greater therapeutic efficacy against OC cells. The drawbacks of traditional chemotherapy, such as poor absorption along with non-specific toxicity, could be addressed by this tailored approach. Our research opens the door for the development of more individualized and effective alternative treatments for OC patients by more efficiently and specifically delivering curcumin to OC cells.