Nanopartículas poliméricas funcionalizadas con dermatán sulfato para la distribución específica de compuestos bioactivos

The incidence of colorectal cancer (CRC) has increased among people under 40, attributed to lifestyle changes and the lack of preventive screenings. 5-Fluorouracil (5- FU) remains the standard treatment; however, its prolonged use is limited by the emergence of resistance, influenced by the presence of cancer stem cells (CSCs) and the activation of signaling pathways such as NF?B. The CD44 receptor plays a crucial role in CRC, being considered a CSCs marker. This study aims to formulate nanoparticles (NPs) of dermatan sulfate (DS) and chitosan, loaded with the anti-inflammatory tripeptide IRW and 5-FU, to achieve their selective distribution. These formulations selectively interact with tumor cells, CSCs, and endothelial cells (ECs) via DS and CD44. IRW loaded NPs sensitize tumor cells to 5-FU treatment by inhibiting the NF?B pathway, increasing its effectiveness, and selectively targeting injured ECs, reversing their activation. Additionally, 5-FU NPs effectively deliver the drug to tumor cells, allowing the drug to exert its antitumor function. In conclusion, this work presents an innovative approach to improving CRC treatment, targeting both tumor cells and CSCs, offering new strategies to address 5-FU tolerance and its side effects.