Synthesis and characterization of NIR-sensitive curcumin-gelatin nanoparticles for targeted drug delivery in 3D colon cancer.

Curcumin (CUR) exhibits potent anti-cancer effects; however, its poor water solubility limits its clinical use. This study explores gelatin nanoparticles (GelNPs) as nanocarriers to improve curcumin delivery. We aimed to enhance the release and efficacy of photosensitive curcumin-loaded GelNPs (Cur-GelNPs) using infrared (IR) light-induced localized hyperthermia in a 3D co-culture cancer model. Cur-GelNPs were synthesized and characterized via DLS, FTIR, STEM, Raman, HPLC, and DSC. Cytotoxicity, migration, invasion, apoptosis, and drug resistance were assessed using MTT, Transwell, Hoechst/PI staining, and Rho123 assays, respectively. Optimal results were achieved by IR treatment at 38 °C for 30 s. Cur-GelNPs localized in the cytoplasm due to curcumin’s natural fluorescence. At 25 µg/ml, Cur-GelNPs significantly reduced the viability, invasion, and migration of colon cancer cells, while promoting apoptosis and mitochondrial damage—more effectively when combined with IR. Importantly, minimal toxicity was observed in healthy cells, suggesting selective cancer targeting. This method enables spontaneous drug-macromolecule binding, reducing time, cost, and labor. Overall, IR-activated Cur-GelNPs represent a promising approach for targeted colon cancer therapy and may offer broader contributions to nanomedicine and drug delivery systems.