Evaluation of bacteriophages applicability as Dickeya chrysanthemis asparaginase carriers

• Grant number: 24/04409-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): August 01, 2024
• Effective date (End): July 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Gisele Monteiro
• Grantee: Igor Lopes da Silva
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Several antineoplastic treatments currently used only explore the compatibility and affinity between the physicochemical nature of the drug and its receptor. However, this type of interaction based on parameters such as presence/absence is responsible for the side effects observed in patients undergoing chemotherapy, as for different types of cancer, it is noted that tumor cells are distinguished from healthy ones not due to the nature, but to the number of expressed receptors. This phenomenon attributes considerable complexity to the treatment of neoplasms, and consequently drives studies aimed at developing technologies that constrain the drug-receptor interaction to the quantitative aspect of tumor phenotypes. In this area, multivalent platforms for drug delivery are especially promising, such as those that associate proteins with bacteriophages. Within this perspective, the present work aims to investigate how the association of Dickeya chrysanthemi asparaginase (erwinase - biopharmaceutical used in the treatment of acute lymphoblastic leukemia) with the M13 bacteriophage capsid alters the original cytotoxicity of the drug. To this end, tests will be carried out aiming to determine the specific activity and enzymatic kinetics, as well as the cytotoxicity on tumor and healthy cells, of the asparaginase displayed by the phage.