Background: Colorectal cancer is a prevalent and lethal gastrointestinal malignancy, while doxorubicin-based chemotherapy is limited by systemic toxicity and drug resistance. Biocompatible nanocarrier systems may improve therapeutic efficacy and reduce adverse effects.



Objective: This study aimed to fabricate sodium alginate-based nanofibers loaded with doxorubicin and evaluate their physicochemical characteristics, cytotoxic effects, and associated molecular responses in colorectal cancer cells.



Methods: Doxorubicin-loaded alginate nanofibers were fabricated by electrospinning and crosslinked with calcium chloride. Morphological and structural properties were characterized using scanning electron microscopy (SEM) and X-ray diffraction (XRD). Cytotoxicity was evaluated using the MTT assay in HT-29 colorectal cancer cells and HUVEC normal endothelial cells. Expression levels of AKT, MAPK p38α, and IKB were analyzed by quantitative real-time PCR.



Results: SEM revealed fiber-like structures with aggregated and irregular regions, with morphological alterations following doxorubicin loading. The nanofibers induced a concentration-dependent reduction in HT-29 cell viability, whereas HUVEC cells showed relatively higher viability. Molecular analysis demonstrated downregulation of AKT and upregulation of MAPK p38α and IKB in treated HT-29 cells, suggesting modulation of survival- and stress-related signaling pathways.



Conclusion: Doxorubicin-loaded alginate nanofibers showed promising anticancer activity against HT-29 cells while relatively preserving HUVEC viability. These findings support their potential as an experimental drug delivery platform. However, controlled or sustained doxorubicin release cannot be established from the present data and requires dedicated in vitro release studies with cumulative release profiling and kinetic modeling.