Neoadjuvant Hyperthermia Combined with Hybrid Nanoarchitectures Enhances Chemoradiotherapy Efficacy in Head and Neck Carcinoma

Head and neck squamous cell carcinomas are characterized by a high incidence of recurrence, especially in patients with locally advanced disease. Standard treatment strategies can be associated with severe side effects to healthy tissues that can negatively impact the patient's quality of life. Hyperthermia (HT) is a noninvasive treatment modality that has improved the effectiveness of chemotherapy (CT) and/or radiotherapy (RT) for the management of some solid neoplasms. In this context, the association of this approach with rationally designed nanomaterials may further enhance the treatment outcome. In this study, we demonstrate the enhanced effect of neoadjuvant HT in combination with hybrid nanoarchitectures enclosing a cisplatin prodrug (NAs-CisPt) and RT. All the treatments and their combinations have been fully evaluated by employing standardized chorioallantoic membrane tumor models of HPV-negative head and neck carcinoma. An improved tumor-shrinking effect was observed by the administration of the trimodal treatment (HT/NAs-CisPt/RT), which also highlighted a significant increase in apoptosis. Our findings demonstrate that the combination of HT with nanotechnology-based CT and RT in a certain order enhances the in vivo treatment outcome. On a broader basis, this study paves the way for the next exploration of noninvasive treatment approaches for the clinical management of oral cancer based on innovative strategies.