Targeted therapeutic strategy for oral squamous carcinoma using celecoxib-loaded GABA/wheat gluten-alginate nanocarrier hydrogel with glutathione down-regulation and enhanced CCND2-mediated apoptosis.

The intricate architecture of the oral cavity results in insufficient surgical excision of oral squamous cell carcinoma (OSCC) potentially increasing the risk of metastasis and recurrence during treatment. In situ generating injectable hydrogels, characterized by minimally invasive methods, encapsulating stability, and pH-responsive breakdown have emerged as viable delivery systems. Herein, we aim to explore a particular therapeutic modality involving the use of celecoxib-loaded GABA/wheat gluten‑sodium alginate (SA/WG-GABA+COX(40)) nanocarriers in enhancing apoptosis of OSCC (HSC-3 & SCC-25). Eventually, drug release profiles show that loaded COX and GABA demonstrated 96.04% and 98.1% at 7.2 pH. Interestingly, crucial experimental techniques like MTT assay, AO/EB staining, DAPI labeling for SCC-25, and HSC-3 displayed the highest cell lysis percentages of 86.5% and 93.3%. Notably, OSCC cell proliferation and migration and cell multiplications were limited with formulated WG/SA-GABA+COX(40) which was evident from In vitro ROS assay, flow cytometry, and JC-1 analysis. In vivo histology, blood serum biochemistry, and tumor examination in xenograft nude mice demonstrated that SA/WG-GABA+COX(40) mice reduced HSC-3 tumor cell proliferation. Downregulation of glutathione and activation of CCND2 signaling pathway caused HSC-3 OSCC cell death. Henceforth, present findings offer an advanced drug delivery method for targeted chemotherapy in treating OSCC.