Bovine serum albumin functionalized graphitic carbon nitride nanosheets embedded in PVA/PVP film for pH-responsive targeted anticancer drug delivery and release kinetics

In this study, we synthesized bovine serum albumin-functionalized graphitic carbon nitride nanosheets (GCNS@BSA) and subsequently embedded them in a PVA/PVP blend to form a nanocomposite film (GCNS@BSA@PVA/PVP) for pH-responsive release of the anticancer drug 5-fluorouracil (5-FU). The functionalization enhanced its biological activity and drug-binding capability, and was confirmed through characterization techniques, including Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Photoluminescence (PL), X-ray Photoelectron Spectroscopy (XPS), and Transmission Electron Microscopy (TEM). FTIR revealed protein–nanosheet interactions by demonstrating peak broadening and shifting. Raman spectra exhibited GCNS characteristic bands and the phenylalanine band. XRD analysis showed a reduction in crystalline structure upon functionalization, attributed to the incorporation of amorphous protein domains. PL indicated altered optical properties, resulting in a red shift due to functionalization. XPS analysis revealed an O 1 s peak and a change in elemental composition, corroborating the introduction of oxygenated functional groups. TEM demonstrated an increase in particle size upon functionalization. The cytotoxicity assay showed a 28% reduction in HeLa cell survival as the concentration of 5-FU loaded in GCNS@BSA@PVA/PVP increased from 25 to 100 µg/mL. Drug release studies revealed cumulative release of 59.32% at pH 5.5 and 63.8% at pH 4.0, approximately 47.5% and 57.5% higher than that at pH 7.5 (40.26%). Kinetic modeling indicated that the release followed the Higuchi model, suggesting a Fickian diffusion-controlled mechanism. These results demonstrate that GCNS@BSA-based nanocomposite films offer a promising approach for pH-responsive, anticancer drug delivery, improving therapeutic outcomes and minimizing side effects in cancer treatment.