Green Synthesis of Silver Nanoparticles: Enhancing Cisplatin Binding to Biomolecules for Improved Drug Delivery and Therapeutic Synergy

Cisplatin and other anticancer drugs face challenges such as systemic toxicity and drug resistance, necessitating novel delivery strategies. Nanoparticles have revolutionized drug delivery by enhancing the efficacy and bioavailability of therapeutic agents. In this study, silver nanoparticles (AgNPs) were green-synthesized using Chromolaena odorata (CO) and characterized using UV-Vis spectroscopy, Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDS), x-ray diffraction (XRD), thermogravimetric analysis (TGA), and transmission electron microscopy (TEM). The interactions of Co-AgNPs, cisplatin, and their combination with biomolecules calf thymus DNA (ctDNA), bovine serum albumin (BSA), and human serum albumin (HSA) were assessed for complex formation and structural alterations in the biomolecules. UV-Vis spectroscopy revealed surface plasmon resonance at 441 nm. SEM analysis indicated a near-Gaussian size distribution with a mean diameter of 0.44 μm, while TEM confirmed the predominantly spherical morphology and polydispersity of the AgNPs within a size range of 10.5-32.9 nm. XRD confirmed a face-centered cubic (FCC) crystalline structure with an average size of 15.57 nm, and EDS indicated the presence of silver, chlorine, oxygen, and nitrogen in the nanoparticle composition. TGA demonstrated the thermal stability of the nanoparticles up to 220°C. Bioassay experiments showed that AgNPs and cisplatin individually interacted with ct-DNA to form stable complexes; the combined AgNP-cisplatin system induced significant conformational changes in the DNA structure, indicating a synergistic effect. Similarly, BSA binding studies revealed stable complex formation with both AgNPs and the AgNP-cisplatin combination, causing pronounced conformational changes in the protein. For HSA, the combination exhibited enhanced binding efficiency compared to individual agents, suggesting improved transport and bioavailability potential. Moreover, molecular docking studies demonstrated that the combined AgNP-cisplatin system exhibited the lowest E_total of -254 kcal/mol, compared to -223.35 kcal/mol for AgNPs and -112.30 kcal/mol for cisplatin alone. This indicates that the combined system interacts more strongly with ct-DNA, likely within the minor groove, displaying enhanced binding affinity.