Title : pH-responsive drug release of 5-fluorouracil using CuInZnS/ZnS as therapeutic drug carriers
Abstract:
Heavy metal-free quaternary semiconductor nanoparticles have recently emerged as a promising agent for biomedical applications owing to their tunable optical properties, enhanced biocompatibility and reduced toxicity. In this study, Cu–In–Zn–S (CIZS) nanoparticles were synthesized through a controlled hydrothermal method and subsequently passivated with a ZnS shell to form CIZS/ZnS core/shell nanostructures with improved optical stability and surface characteristics. The optical, morphological and structural properties were systematically investigated using photoluminescence (PL) spectroscopy, UV-Visible spectroscopy, Fourier-transform infrared spectroscopy (FTIR), high-resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), dynamic light scattering (DLS), and zeta potential analysis, confirming the formation of stable, monodispersed, and highly luminescent nanostructures. For therapeutic application, the anticancer drug 5-fluorouracil (5-FU) was conjugated onto the CIZS/ZnS nanoparticles using two distinct approaches: (i) with crosslinkers (EDC/NHS) mediated covalent coupling and (ii) without crosslinkers (non-covalent) adsorption. The drug loading efficiency (DLE: ~91.5%) and drug loading capacity (DLC: ~15.8%) are higher in the crosslinker-assisted system compared to the non-crosslinked system, indicating enhanced binding affinity and improved stability of the drug-nanoparticle complex. In vitro drug release studies performed at physiological (pH 7.4), and acidic (pH 5.5) conditions revealed a pH-responsive release behaviour, with significantly higher drug release observed under acidic conditions in both cases, imitating the tumour environment. This suggests the potential of the developed system for targeted and controlled drug delivery. The biocompatibility and therapeutic efficiency of the nanoparticles were evaluated using the MTT Assay on Huh-7 liver cancerous cells. The core/shell nanoparticles exhibited higher biocompatibility (IC50 is higher) compared to bare CIZS cores, while drug-conjugated nanostructures showed significantly increased cytotoxicity, confirming effective drug delivery and therapeutic action. Overall, CIZS/ZnS nanoparticles show significant potential as a multifunctional system for pH-responsive drug delivery and cancer therapeutics.
