Curcumin-Loaded Cellulose Nanofibers for Breast Cancer Therapy: A Multiscale Computational and Experimental Evaluation.

Purpose: Efficient nanocarrier design for tumour targeting requires understanding drug binding, release, and membrane interactions. This study presents the first all-atom molecular dynamics simulations of curcumin-loaded cellulose nanofibers (CNFs) interacting with healthy and breast cancer cell membranes, supported by experimental evaluation. Methods: Simulations were performed on curcumin-loaded cylindrical and planar CNFs docked onto modelled healthy and breast cancer-mimicking lipid bilayers, followed by assessing binding energetics, structural stability, solvent exposure, and molecular mobility. Experimentally, free and curcumin-loaded CNFs were fabricated, characterized, and evaluated for encapsulation efficiency, in vitro release, and cytotoxicity. Results: Computational results showed that both arrangements interacted more favourably with cancer membranes than healthy models. In cylindrical systems, curcumin exhibited reduced mobility, increased localization, and partial penetration into cancer membranes, whereas planar systems favoured continued drug association with the nanocarrier and stronger membrane interaction. According to the experimental results, uniform CNFs achieved 82% encapsulation efficiency and showed biphasic release behaviour. Blank CNFs were biocompatible, while curcumin-loaded CNFs induced concentration- and time-dependent cytotoxicity in MCF-7 cells. Conclusion: Findings highlight the importance of membrane composition and nanofiber arrangement in regulating drug release and therapeutic performance, providing insights for rational nanocarrier design in cancer drug delivery.