ArticleInternational journal of nanomedicine2026
Cyclodextrin-Based Nanocarriers for 5-Fluorouracil: Cholesteryl Modification Enhances Antitumor Activity Against Colorectal Cancer Cells.
Article in International journal of nanomedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: The objective of this study is to evaluate the biological activity of cholesterol-modified cyclodextrin (CD21chol) complexes with 5-fluorouracil (5-FU) prepared at different molar ratios (1:1, 1:2, and 1:3) and to identify the most potent anticancer formulation. Methods: The inclusion complexes of CD21chol:5-FU were prepared at different molar ratios (1:1, 1:2, and 1:3) and initially characterized based on their physicochemical properties, such as increased negative surface charge and particle size. Subsequently, the biological activity was investigated in the human colorectal cancer cell line DLD-1 by analyzing cell viability, metabolic activity, membrane integrity, and apoptosis (activation of caspases 3/7, 8, and 9). Cytotoxicity was also measured in non-tumorigenic fibroblasts and cardiomyocytes. Results: The complexation with 5-FU resulted in a shift toward more negative zeta potential values, with the 1:3 CD21chol:5-FU system showing the greatest change and improved physicochemical stability. Particle size analysis revealed a reduction in hydrodynamic diameter at lower drug ratios (1:1 and 1:2), followed by an increase at the 1:3 ratio. Biologically, the 1:3 complex exerted the strongest cytotoxic effect against DLD-1 cells, reducing metabolic activity and cell viability by over 60%, increasing LDH release, and significantly activating caspases 3/7, 8, and 9, indicating engagement of both intrinsic and extrinsic apoptotic pathways. In contrast, only moderate toxicity was observed in CCD-1079SK fibroblasts and H9c2(2-1) cardiomyocytes. Conclusion: The results indicate that CD21chol-based delivery systems enhance the anticancer activity of 5-FU. The 1:3 complex appears to be the most promising candidate for further development in colorectal cancer therapy.
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