Versatile cobalt-glycerate nanoplatform for MR-guided neoadjuvant photo-therapy of oral squamous cell carcinoma

Adjuvant treatments following surgical resection of oral squamous cell carcinoma (OSCC) are essential to reduce local recurrence. Current adjuvant treatments, such as radio- and/or chemo-therapy, can cause radiation-induced damage or systemic toxicity. To improve the effects of adjuvant treatments and prognosis of OSCC, a novel multi-functional cobalt-glycerate nano-sheet (CoG-NS) platform is developed that enhances magnetic resonance imaging (MRI) and provides synergistic anti-tumor effects via photothermal/photodynamic therapy (PTT/PDT). Laser irradiation of CoG-NSs induces hyperthermia and activates their catalytic production of oxygen (O2), as well as toxic reactive oxygen species (ROS) from hydrogen peroxide (H2O2) inside solid tumors, disrupting hypoxia in the tumor microenvironment (TME). These combined effects synergistically inhibit OSCC growth in vitro and in vivo. Activation of CoG-NSs in tumor cells can also lead to decreased expression of heat shock protein 70 (HSP70), apoptotic protein Bcl-2, and cell cycle protein Cyclin D1, thus limiting tumor proliferation and inducing apoptotic effects. After MRI-guided tumor reduction surgery in animal model, the targeting and accumulation of CoG-NSs in tumor cells combined with 808 nm laser irradiation enables effective suppression of local recurrence and significant improvement of the survival rate of OSCC tumor-bearing animals. These results reveal the potential of CoG-NSs as a less damaging and lower toxicity neo-adjuvant therapy, which is beneficial especially for patients susceptible to radiation or intolerant to drug toxicity.