A multifunctional hydrogel dressing for wound healing and in vitro cytotoxicity against breast cancer cells: association with GRP78 expression.

Investigating molecular pathways associated with breast cancer progression is important for improving post-surgical therapeutic strategies. Since certain chemotherapeutic agents can activate the unfolded protein response (UPR), with glucose-regulated protein 78 (GRP78) acting as a key regulator of this pathway, this study aimed to develop a post-surgical hydrogel nanocomposite and evaluate its anticancer activity together with its potential effects on GRP78 localization. Chitosan nanoparticles (CsNPs) were synthesized and incorporated into a hydrogel matrix, and the resulting system was characterized using imaging and particle-sizing techniques. Biological evaluations, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on mouse fibroblast NIH/3T3 cells and hemolysis assay, demonstrated acceptable biocompatibility and hemocompatibility of the developed hydrogels. Anticancer investigations in Michigan Cancer Foundation-7 (MCF-7) cells, including MTT assay, apoptosis analysis, intracellular ROS measurement, mitochondrial membrane potential assessment, and caspase activity assay, revealed significant anticancer effects of the nanocomposite. Mechanistic analysis of GRP78 expression further suggested that the hydrogel may promote GRP78 translocation from the cytoplasm to the tumor cell surface, accompanied by increased GRP78 expression, indicating a possible association between GRP78-mediated cellular stress responses and the observed anticancer activity. Overall, these findings support the potential of the developed post-surgical hydrogel nanocomposite as a localized therapeutic platform for breast cancer treatment; however, any direct effects on metastatic behavior remain to be confirmed through dedicated metastasis-related assays.