Posted by This study (1) aims to build on previously published results that characterized cholesteryl-modified β-cyclodextrin (CD21chol) as a carrier for 5-fluorouracil. (2) This approach appears to be a highly promising solution. Cyclodextrin decorated with 21 cholesteryl moieties (CD21chol) retained thermally stable and possessed the ability to form inclusion complexes, making it an excellent candidate for drug delivery applications. In a recent study, cholesteryl-modified cyclodextrin system was investigated as a carrier for hydrophobic anticancer agents such as doxorubicin, demonstrating their ability to form stable inclusion complexes and exhibit enhanced biological activity. (3) The present work (1) extends this system toward a structurally distinct, small and highly hydrophilic drug, 5-fluorouracil, whose interaction with cyclodextrin-based carriers remains less well understood. This allowed to evaluate the versatility and limitations of the previously developed delivery platform beyond strongly interacting guest molecules. These complexes facilitate the delivery of therapeutic agents directly to cancer cells, thereby reducing their toxicity to non-targeted cells. To this end, the compatibility and cytotoxic potential of the complexes were examined using various methods. The complexes with 5-fluorouracil were evaluated against representatives of normal cells (CCD-1079Sk fibroblasts and H9c2(2–1) cardiomyocyte cells) and colorectal cancer cells (DLD-1 line). The CD21chol:5-FU displayed robust in vitro antineoplastic efficacy, evidenced by its capacity to diminish the viability and proliferation of cancerous cells by disrupting the plasma membrane and inducing apoptosis, as demonstrated by the analysis of caspase pathways. According to the data presented, the cholesteryl-modified cyclodextrin carrier for 5-FU shows considerable promise as a therapeutic nanocarrier, with the potential to modulate 5-FU activity, reduce dosage requirements, and overcome drug resistance.
Doxorubicin and 5-fluorouracil
(1) Skonieczna B, Maliszewski B, Wasiluk N, Car H, Wilczewska AZ, Misiak P, Niemirowicz-Laskowska K. Cyclodextrin-Based Nanocarriers for 5-Fluorouracil: Cholesteryl Modification Enhances Antitumor Activity Against Colorectal Cancer Cells. Int J Nanomedicine. 2026;21:583792
https://doi.org/10.2147/IJN.S583792
(2) Misiak P, Maliszewski B, Pawłowska Z, Ignaczak A, Wilczewska AZ. Encapsulation of 5-fluorouracil in cholesteryl-modified cyclodextrin: thermal, spectral, and computational assessment of drug inclusion efficiency. J Mater Chem B. 2024;12(29):7063–7075. https://doi.org/10.1039/D4TB00496E
Maliszewski B, Ignaczak A, Skonieczna B, et al. Targeted delivery of doxorubicin via cholesteryl-modified cyclodextrin: antitumor activity in breast, ovarian, and cervical cancer cell lines. Chem Biol Interact. 2026;432:112062. https://doi.org/10.1016/j.cbi.2026.112062