Head and neck squamous cell carcinomas (HNSCC) have a high prevalence and lethality, mainly due to: i) their late diagnosis, ii) the low availability of therapeutic alternatives for HNSCC patients and iii) the acquisition of resistance to conventional therapies.The membrane receptor TSPAN1 is an oncogenic protein involved in proliferation, migration and metastasis in several cancers. We have recently described TSPAN1 key role in chemoresistance, as TSPAN1 depletion sensitizes HNSCC cells to cisplatin (CDDP) treatment.

 Through a virtual screening based on three different docking simulation programs and according to the Specs database, 2 drugs capable of blocking TSPAN1 were unveiled and patented showing promising results in mice. However, these drugs have high hydrophobic properties, thus compromising their biodistribution. Here we will focus on the best of these 2 drugs. The ultimate goal of this Project is to combat HNSCC resistant tumors to conventional therapies (CDDP, docetaxel-DTX) by developing a ground-breaking therapy based on new patented drugs encapsulated with CDDP or DTX into magnetoplasmonic nanocapsules (MAPSULES), which have already shown the capacity to amplify the local chemotherapy effects by external opto-magnetic actuation.

 This technology will enable: i) improving the drug circulation, ii) minimizing the systemic side effects of free drugs and iii) locally enhancing the therapeutic effects specifically in the tumor in the mission to annihilate biopsy-derived chemoresistant HNSCC. The biomedical potential will be demonstrated by the enhanced therapeutic efficacy of the MAPSULES with respect to the free or encapsulated drug, in vitro and in a HNSCC mice model derived from patients. Demonstration of clinical benefits by the MAPSULES therapy will produce a transformational impact in current solid tumor treatments by offering an effective therapy with minimal side effects and cost effective, that can be readily applied to other drugs and solid tumors