Chitosan modification is crucial for advancing biomedical applications. This study discusses the fabrication and characterization of new chitosan bead derivatives. The new hydrogel CSE was synthesized by reacting chitosan beads with epichlorohydrin which was further modified with isonicotinic acid hydrazide (INH) using microwave irradiation to produce CSEH hydrogel. The nanohydrogel NCSEH was fabricated by reacting CSEH with sodium tripolyphosphate (TPP) via ionic gelation technique. In addition, CSEH hydrogel loaded Ag and ZnO nanoparticles to give the nanocomposites CSEH-Ag NPs and CSEH-ZnO NPs respectively. The new chitosan bead derivatives were characterized using various instrumental analysis techniques including elemental analysis, Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Thermogravimetric Analysis (TGA), and Energy Dispersive X-ray Spectroscopy (EDX). The nanohydrogel NCSEH showed the highest thermal stability. TEM analyses confirmed the nano-scale dimensions of NCSEH, CSEH-Ag NPs, and CSEH-ZnO NPs with particle sizes ranging from 4.46 to 125 nm. EDX and SEM profiles of the modified CSEH-Ag NPs and CSEH-ZnO NPs showed distinct signals for Ag and Zn atoms, respectively. Elemental analysis revealed 0.36% silver for CSEH-Ag NPs and 5.90% zinc for CSEH-ZnO NPs confirming the successful formation of the nanocomposites. The anticancer activity of the new chitosan bead derivatives CSEH, NCSEH, CSEH-Ag NPs, and CSEH-ZnO NPs were evaluated against A-549 lung and HCT-116 colon cancer cell lines. The CSEH-ZnO nanocomposite demonstrated the most potent cytotoxic effect, exhibiting (IC50) values of 36 ± 1.29 µg/mL against lung cancer cells and 24.99 ± 0.83 µg/mL against colon cancer cells. At concentration 500 μg/mL of CSEH-ZnO nanocomposite demonstrated the highest cell growth inhibition 97.14%, and 98.63% for lung and colon cells respectively. These results suggest that CSEH-ZnO nanocomposite is a promising candidate for targeted cancer therapy.
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