EVALUATION OF THE EFFICACY OF A NANOSYSTEM AND A POLYMERIC HYDROGEL INCORPORATED WITH SOLAMARGINE IN HUMAN GLIOBLASTOMA MODELS

• Grant number: 24/17110-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2025
• End date: April 30, 2028
• Field of knowledge: Health Sciences - Pharmacy - Pharmacognosy
• Principal Investigator: Jairo Kenupp Bastos
• Grantee: Arthur Barcelos Ribeiro
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The complexity of the tumor microenvironment, combined with the genetic heterogeneity and highly invasive nature of GB-IDHwt, makes it one of the most resistant tumors to available antineoplastic therapies. Currently, the standard treatment for GB-IDHwt involves a multimodal approach, which combines surgery for maximal tumor resection with radiotherapy and chemotherapy. However, these interventions have a limited impact on patient survival, often resulting in an unfavorable clinical prognosis. In the search for new therapeutic alternatives for the treatment of GB-IDHwt and in an attempt to minimize the side effects of existing treatments, natural products have emerged in oncology. In this context, this project aims to investigate the antitumor potential of SM, a steroidal alkaloid extracted from plants of the Solanum genus, encapsulated in SLPN and incorporated into a thermo-responsive HG, for the treatment of human GB-IDHwt. The project will address three main experimental fronts: (1) In vitro evaluation of the effects of SM, both isolated and as SLPN-SM, on proliferation, morphology, cell cycle, apoptosis, migration, and invasion in multicellular spheroids of human GB-IDHwt cultured in 3D models; (2) In vivo investigation of the efficacy of SLPN-SM and HG/SLPN-SM in orthotopic models of GB-IDHwt and GB-IDHwt recurrence post-surgical resection, focusing on tumor volume reduction and toxicological aspects; and (3) Study of the therapeutic potential of combining HG/SLPN-SM with EBRT. This project will be carried out in collaboration with renowned researchers in Brazil and France, fostering knowledge exchange and the development of new technologies. The integration of advanced experimental models with technological innovations in NP and HG holds the potential to yield more effective and personalized therapeutic approaches for the treatment of GB-IDHwt. The expected results may significantly contribute to understanding the mechanisms of action of SM in the tumor context and to advancing therapeutic strategies against GB-IDHwt, strengthening scientific research in Brazil and consolidating long-lasting international partnerships.