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Nanoscale metal-organic frameworks for drug delivery to oral cancer

Grant number: 21/14880-9
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): August 01, 2022
Effective date (End): July 31, 2023
Field of knowledge:Health Sciences - Dentistry - Dental Clinics
Principal researcher:Adriana Franco Paes Leme
Grantee:Luciana Daniele Trino Albano
Supervisor abroad: Wenbin Lin
Home Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovações (Brasil). Campinas , SP, Brazil
Research place: University of Chicago, United States  
Associated to the scholarship:18/12194-8 - Immobilization of multiple potential biomarkers, pure and obtained from liquid biopsies, in Metal-Organic Frameworks (MOFs) as biosensors applied in head and neck Cancer diagnosis and prognosis, BP.PD

Abstract

One of the major challenges of oral cancer is the late diagnosis, which affects the therapeutic treatment with a negative influence on prognosis and, consequently, survival rate. The standard treatments include surgery, radiotherapy, and/or chemotherapy. However, these treatments often result in numerous adverse side effects and multi-drug resistance, which leads to a poor therapeutic response in many cases. To overcome these limitations, nanotechnology-based approaches are used to ensure precise therapy of cancer and to overcome drug resistance. Nanoscale metal-organic frameworks (nMOFs) have emerged as an attractive class of nanomaterials for drug delivery to oral cancer due to their good biocompatibility and high drug loading capacity. Large-pore nMOFs, like MIL-100(Fe), can be post-synthetically modified with drug candidates of interest for targeted therapy. A promising therapeutic target in oral cancer is Leukotriene A4 hydrolase (LTA4H), which is expressed in oral squamous cell carcinoma (OSCC). One hypothesis is that the relationship between LTA4H and cancer development may be related to its role in the biosynthesis of LTB4, a metabolic product of arachidonic acid. Consequently, molecules that interfere with the biosynthesis pathway of LTB4 through LTA4H might inhibit cancer progression. Ubenimex and tosedostat are aminopeptidase inhibitors that target LTA4H and have shown good results in cancer therapy studies. Therefore, the objective of this project is to develop a drug delivery system, based on nMOFs, for the delivery of the drugs ubenimex and tosedostat to oral cancer cells, to verify the role of these drugs as inhibitors of LTA4H, and to determine whether LTA4H could serve as a therapeutic target for oral cancer. (AU)

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