Shiga toxin-targeted gold nanorods for head-neck cancer photothermal therapy in clinical samples

Abstract Background A great challenge in nanomedicine, and more specifically in theranostics, is to improve the specificity and selectivity of nanomaterials towards target tissues or cells. The topical use of nanomedicines as adjuvants to systemic chemotherapy can significantly improve the survival of patients affected by localized carcinomas, reducing the side effects of traditional drugs and preventing local recurrences.Results Here we have used the Shiga toxin, to design a safe, high-affinity protein-ligand (ShTxB) to bind the globotriaosylceramide receptor (GB3) that is overexpressed on the surfaces of preneoplastic and malignant cancer cells in head and neck tumors. We find that ShTxB functionalized gold nanorods are efficiently retrotranslocated to the GB3 positive cell cytoplasms. After 3-10 minutes of laser radiation with a wavelength resonant with the AuNR longitudinal localized surface plasmon, the death of the targeted cancer cells is activated. Both preclinical models and patient biopsy cells show the non-cytotoxic nature of these functionalized nanoparticles prior to light activation and their treatment selectivity.Conclusions These results show how the topical use of nanomedicines targeted by natural ligands can represent an effective treatment for aggressive localized cancers, such as squamous cell carcinoma of the head and neck.