Post-Surgery Healing Hydrogel Dressing with Anti-Metastatic Potential and Its Effects on Breast Cancer Cell Metastasis and Endoplasmic Reticulum Localization of Grp78

Investigating the molecular mechanisms underlying metastasis is crucial for addressing metastatic breast cancer. Two common chemotherapy drugs, doxorubicin and paclitaxel, partially work by triggering the unfolded protein response (UPR), with glucose-regulated protein 78 (GRP78) serving as a significant regulator of this process. This research aimed to develop a post-surgery hydrogel nanocomposite with anti-metastatic properties and evaluate its effects on breast cancer metastasis and GRP78 localization. Chitosan nanoparticles (CsNPs) were produced and integrated into a hydrogel, which was then analyzed using various imaging and sizing methods.Biological evaluations using MTT assay against mouse fibroblast NIH/3T3 and hemolysis assay showed that the hydrogels' biocompatibility and hemocompatibility. Anticancer evaluations (MTT assay, apoptosis analysis, intracellular ROS detection, mitochondrial potential measurements, and caspase activity assay against MCF-7 cells) revealed potent anticancer potential of the structure. Mechanistic studies using quantitative analysis of GRP78 expression showed that the hydrogel promotes GRP78 translocation from the cytoplasm to the tumor cell surface, enhancing GRP78 expression and supporting anticancer and anti-metastatic effects via UPR activation. These findings suggest that the developed hydrogel nanocomposite may serve as a multifunctional anti-metastatic strategy for breast cancer treatment in the post-surgical context.