Neoadjuvant Hyperthermia\nCombined with Hybrid Nanoarchitectures\nEnhances Chemoradiotherapy Efficacy in Head and Neck Carcinoma

Head and neck squamous cell carcinomas are characterized\nby a high\nincidence of recurrence, especially in patients with locally advanced\ndisease. Standard treatment strategies can be associated with severe\nside effects to healthy tissues that can negatively impact the patient’s\nquality of life. Hyperthermia (HT) is a noninvasive treatment modality\nthat has improved the effectiveness of chemotherapy (CT) and/or radiotherapy\n(RT) for the management of some solid neoplasms. In this context,\nthe association of this approach with rationally designed nanomaterials\nmay further enhance the treatment outcome. In this study, we demonstrate\nthe enhanced effect of neoadjuvant HT in combination with hybrid nanoarchitectures\nenclosing a cisplatin prodrug (NAs-CisPt) and RT. All the treatments\nand their combinations have been fully evaluated by employing standardized\nchorioallantoic membrane tumor models of HPV-negative head and neck\ncarcinoma. An improved tumor-shrinking effect was observed by the\nadministration of the trimodal treatment (HT/NAs-CisPt/RT), which\nalso highlighted a significant increase in apoptosis. Our findings\ndemonstrate that the combination of HT with nanotechnology-based CT\nand RT in a certain order enhances the in vivo treatment outcome.\nOn a broader basis, this study paves the way for the next exploration\nof noninvasive treatment approaches for the clinical management of\noral cancer based on innovative strategies.