Shiga Toxin-B Targeted Gold Nanorods for Local Photothermal Treatment in Oral Cancer Clinical Samples

Abstract

Elena Navarro-Palomares,1 Lorena García-Hevia,1 Jesús Galán-Vidal,2 Alberto Gandarillas,2 Fe García-Reija,3 Ana Sánchez-Iglesias,4,5 Luis M Liz-Marzán,4,5 Rafael Valiente,1,6 Mónica L Fanarraga1 1The Nanomedicine Group, Valdecilla Health Research Institute IDIVAL, Universidad de Cantabria, Santander, 39011, Spain; 2Cell Cycle, Stem Cell Fate & Cancer Laboratory, Valdecilla Health Research Institute IDIVAL, Santander, 39011, Spain; 3Oral and Maxillofacial Surgery Unit, Valdecilla Hospital HUVM, Santander, Spain; 4CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), and CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), San Sebastián, 20014, Spain; 5Ikerbasque, Basque Foundation for Science, Bilbao, 48009, Spain; 6Dpt. Applied Physics, Facultad de Ciencias, Universidad de Cantabria, Santander, 39005, SpainCorrespondence: Mónica L Fanarraga; Lorena García-Hevia, Valdecilla Health Research Institute IDIVAL, University of Cantabria, Avda Herrera Oria s/n, Santander, 39011, Spain, Tel [phone] Ext. 74101, Email [email protected]; [email protected]: A great challenge in nanomedicine, and more specifically in theranostics, is to improve the specificity, selectivity, and targeting 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.Methods: 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 the head and neck tumors.Results: We find that ShTxB functionalized gold nanorods are efficiently retrotranslocated to the GB3-positive cell cytoplasms. After 3 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 murine models and patient biopsy cells show the non-cytotoxic nature of these functionalized nanoparticles before light activation and their treatment selectivity.Discussion: These results show how the use of nanomedicines directed by natural ligands can represent an effective treatment for aggressive localized cancers, such as squamous cell carcinoma of the oral cavity.Keywords: functionalized nanomaterial, natural ligand, nanoparticle targeting, squamous carcinoma, globotriaosylceramide

Keywords

• functionalized nanomaterial
• natural ligand
• nanoparticle targeting
• squamous carcinoma
• globotriaosylceramide.