In Vitro Anticancer Activities of Curcumin‐Loaded Copper Oxide–Halloysite Nanotubes Composite

Purpose: This study presents a novel and sustainable approach to cancer therapy by combining halloysite nanotubes (HNTs), green‐synthesized copper oxide (CuO) nanoparticles, and curcumin (CUR). We demonstrate that the green synthesis of CuO nanoparticles, when combined with CUR and incorporated into HNTs, enhances the delivery and anticancer effects of CUR. This innovative complex could address some of the critical limitations of current anticancer therapies such as poor pharmacokinetics and drug resistance by providing a controlled release mechanism and leveraging the benefits of combination therapy. Methods: We synthesized CuO using green synthesis with lemon peel extract and used this synthesized CuO to formulate a complex with HNT and CUR (CHC). Comprehensive characterization was conducted using UV‐visible spectroscopy, scanning electron microscopy‐energy‐dispersive X‐ray spectroscopy (SEM–EDX), X‐ray diffraction (XRD), thermogravimetric analysis (TGA), and Fourier‐transform infrared spectroscopy (FTIR). We also examined the release kinetics of the formulation. In vitro experiments were performed to evaluate the anticancer effects of the complex on HMVII, HepG2, and MCF‐7 cancer cell lines. In addition, an in silico docking assessment and a 10 ns molecular dynamics simulation were conducted to determine the interaction between CUR and HNTs. Results: The characterization of HNTs loaded with CUR showed a drug loading efficiency of 3%–5% and an encapsulation efficiency of 15%–20%. Drug release kinetics were best described by the Hixson–Crowell model for CHC‐50 and CHC‐20, with R 2 = 0.9897 and R 2 = 0.9900 respectively. CHC‐10 fit the Higuchi model ( R 2 = 0.8838), while free CUR fit the Korsmeyer–Peppas model ( R 2 = 0.9212). The formulations demonstrated significant anticancer effects across all tested cell lines, with CHC‐10 showing the lowest IC 50 value of 10.43 μg/mL. The CHC formulations exhibited enhanced delivery and maintained significant anticancer activity compared to CUR across HepG2, MCF‐7, and HMVII cell lines, with lower IC50 values after UV exposure. Molecular docking analysis revealed a CUR–HNT binding score of −3.803, with the complex remaining stable over a 10 ns simulation. Conclusion: This study demonstrates the successful integration of green‐synthesized CuO nanoparticles with CUR‐loaded HNTs as a novel approach to cancer therapy. The enhanced anticancer effects of the CHC‐10 formulation, coupled with the complex’s stability, suggest significant potential for improving cancer treatment outcomes. This innovative, sustainable approach addresses key limitations of current therapies, potentially offering more effective and patient‐friendly treatments with reduced side effects. Our findings pave the way for further development of targeted, environmentally conscious cancer therapies.