NANOCARRIERS FOR THE OPTIMIZED TARGETED DELIVERY FOR GENETIC THERAPIES APPLIED TO THE PANCREATIC CANCER

• Grant number: 24/00166-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2024
• End date: May 31, 2026
• Field of knowledge: Physical Sciences and Mathematics - Physics - Condensed Matter Physics
• Principal Investigator: Valtencir Zucolotto
• Grantee: Thaiane Alcarde Robeldo
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

Among the causes of cancer-related death worldwide, pancreatic cancer occupies a prominent position, characterized by its high recurrence rates and resistance to treatments. Surgical resection is still the main treatment, followed by chemotherapy and radiotherapy. Due to the highly desmoplastic characteristics of the tumor microenvironment, it makes it impossible for drugs to be effective in neoplastic tissue. RNA-induced genomic silencing (iRNA) therapy is a treatment based on the regulation of disease-causing or disease-promoting target genes, especially those that are not amenable to conventional therapies. The insulin-like growth factor receptor (IGF-1R) is a strong candidate for actively targeting gene silencing therapy in pancreatic tumor cells, as it is responsible for activating the signaling cascade of the phosphatidylinositol 3-kinase pathways (PI3K), AKT, Rac, and mitogen-activated protein kinase (MAPK). Cationic liposomes are a group of nanoparticles that have demonstrated an advantage in gene delivery, capable of protecting iRNA molecules against enzymatic degradation and recognition by the immune system. When coated by cell membranes, they can also present greater targeted transport efficiency. In this context, this Postdoctoral Project aims at the development and application of liposomal nanoparticles coated with the plasma membrane of pancreatic tumor cells, as a new targeted delivery tool for gene silencing, for potential therapy for pancreatic cancer.