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

Introduction 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.Acknowledgments: We are grateful to Débora Muñoz for her technical support and the IDIVAL microscopy service. MLF acknowledges ISCIII Grants PI19/00349 and DTS19/00033, co-funded by the European Regional Development Fund, “Investing in your future”; COST action Nano2Clinic CA17140, and IDIVAL for the PREVAL16/02, INNVAL20/13 and INNVAL21/ 19 projects. L.M.L.M. acknowledges funding from the European Research Council (ERC AdG 787510, 4DbioSERS) and the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency (Grant No. MDM-2017- 0720). RV acknowledges financial support from Spanish Ministerio de Ciencia, Innovación y Universidades (PGC2018- 101464-B-I00) and HIPERNANO RED2018-102626-T). A.G. acknowledges ISCIII/FIS-FEDER Grant PI20/00880. J. G. acknowledges the predoctoral scholarship from Asociación Española Contra el Cáncer (AECC; Spain), PRDCA19003GALA. Figures 1C, 2A, 3A and 4A have been created with BioRender.co

Monitoring the prevalence of chronic conditions: which data should we use?

<p>Abstract</p> <p>Background</p> <p>Chronic diseases are an increasing threat to people’s health and to the sustainability of health organisations. Despite the need for routine monitoring systems to assess the impact of chronicity in the population and its evolution over time, currently no single source of information has been identified as suitable for this purpose. Our objective was to describe the prevalence of various chronic conditions estimated using routine data recorded by health professionals: diagnoses on hospital discharge abstracts, and primary care prescriptions and diagnoses.</p> <p>Methods</p> <p>The ICD-9-CM codes for diagnoses and Anatomical Therapeutic Chemical (ATC) codes for prescriptions were collected for all patients in the Basque Country over 14 years of age (n=1,964,337) for a 12-month period. We employed a range of different inputs: hospital diagnoses, primary care diagnoses, primary care prescriptions and combinations thereof. Data were collapsed into the morbidity groups specified by the Johns Hopkins Adjusted Clinical Groups (ACGs) Case-Mix System. We estimated the prevalence of 12 chronic conditions, comparing the results obtained using the different data sources with each other and also with those of the Basque Health Interview Survey (ESCAV). Using the different combinations of inputs, Standardized Morbidity Ratios (SMRs) for the considered diseases were calculated for the list of patients of each general practitioner. The variances of the SMRs were used as a measure of the dispersion of the data and were compared using the Brown-Forsythe test.</p> <p>Results</p> <p>The prevalences calculated using prescription data were higher than those obtained from diagnoses and those from the ESCAV, with two exceptions: malignant neoplasm and migraine. The variances of the SMRs obtained from the combination of all the data sources (hospital diagnoses, and primary care prescriptions and diagnoses) were significantly lower than those using only diagnoses.</p> <p>Conclusions</p> <p>The estimated prevalence of chronic diseases varies considerably depending of the source(s) of information used. Given that administrative databases compile data registered for other purposes, the estimations obtained must be considered with caution. In a context of increasingly widespread computerisation of patient medical records, the complementary use of a range of sources may be a feasible option for the routine monitoring of the prevalence of chronic diseases.</p