Ferritin nanoparticles for peptide vaccine delivery: development, characterization, in vitro release studies and in vivo immunogenicity studies

• Grant number: 21/05482-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2022
• End date: June 30, 2023
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Fabiana Testa Moura de Carvalho Vicentini
• Grantee: Camila Machado França de Almeida
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Ferritin is probably the most studied protein after hemoglobin, being investigated since 1937 and very well analyzed in relation to its physiological properties and formation of the mineral nucleus. Nevertheless, more recently, it has been recognized for its potential as a drug carrier system (HE; FAN; YAN, 2019), receiving more attention in the areas of materials science, chemistry, pharmacology, food science and nutrition (LIU et al., 2019) and attracting interest from both the academia and the industry (KIM et al., 2011).Some of its natural characteristics that make its use as a nanostructured delivery system for the delivery of different types of molecules extremely promising are: (1) it is a biological nanoparticle ready to be used; (2) present thermal stability (resisting temperatures up to 80-100 ° C) and pH stability (pH 3-10), small uniform size, biocompatibility, biodegradability and low cost for large scale production; (3) natural ability to encapsulate a series of molecules, due to the presence of highly stable compartments capable of disorganizing and reconstituting the natural shape; (4) be extremely versatile and receptive to both chemical and genetic modifications that can be used to incorporate therapeutic molecules; and finally (5) for being able to undergo modifications capable of making it more modular and responsive to certain stimuli (BELLINI et al., 2014; HE; MARLES-WRIGHT, 2015; KHOSHNEJAD et al., 2018; TESAROVA et al. , 2020; TRUFFI et al., 2016). In this context, the present project proposes to develop and characterize ferritin-based delivery systems for the delivery of a peptide vaccine for use in the treatment of melanoma. The choice of vaccine antigen (EGFrvIII) is justified by its association with tumorigenicity by increased cell proliferation and inhibition of apoptosis, with a high incidence rate in patients with melanoma and the epitope (PEPvIII) specific tumor (CHEN et al., 2018). Thus, the final aim of the present project is to obtain a vaccine formulation capable of breaking the immunosuppression that exists in the tumor environment to generate an effective response against it. Promising results regarding the evaluation of the immunogenicity generated by the administration of these systems will provide future projects designed to evaluate the antitumor efficacy in a melanoma model.