Tannic acid-modified graphene oxide nanoplatform incorporating bortezomib as a combination chemo- and NIR-mediated photothermal oral cancer therapy.

Oral cancer poses a serious disease as it has the highest incidence, and surgical intervention leads to maxillofacial deformation (facial, dental, and jaw disfigurement). Thus, developing efficient therapy is essential. Herein, Bortezomib (BTZ), a proteasomal inhibitor primarily used clinically for the treatment of hematologic cancers, is equally effective in solid tumors and has been explored via a nanomedicine strategy. A graphene oxide-based unique nanoplatform was developed and coated with Tannic Acid (TA) to enhance its dispersibility, achieve superior drug loading via non-covalent binding interactions, including hydrogen bonding and electrostatic interactions, with bortezomib, and improve its anticancer therapeutic response. The developed BTZ@GOT scaffolds formed stable nanoparticles with a size of 142.3 nm, a zeta potential of -2.31 mV, and a BTZ loading of 14.2 %, where the TA coating assisted in the conversion of the sheet-like structure to uniformly dispersed particles. These BTZ@GOT NPs were stable, least hemolytic, and demonstrated targeted release in a low pH environment. Interestingly, BTZ@GOT NPs demonstrated enhanced photothermal efficiency, raising the temperature to 50 ºC. The in vitro therapeutic efficacy study, performed on murine and human oral carcinoma cell lines, MOC2 and FaDu, respectively, demonstrated enhanced accumulation in cells over time, as well as the accumulation of pro-apoptotic factors and reactive oxygen species, leading to mitochondrial damage and ultimately resulting in cancer cell death. Moreover, in vivo studies in MOC2-induced tumor-bearing mice demonstrated a significant upregulation of ER stress markers, including PERK and PDI, as well as remodeling of macrophages, characterized by the upregulation of M1 markers, such as iNOS, TNF-α, and CD86. Thus, BTZ@GOT is an efficient nanotherapy that warrants further exploration for the treatment of oral carcinoma.