siRNA Cancer Therapy: A Novel Nanotechnological Approach Using Albumin Nanoparticles

• Grant number: 24/22512-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2025
• End date: April 30, 2029
• Field of knowledge: Interdisciplinary Subjects
• Principal Investigator: Alioscka Augusto Sousa
• Grantee: Vinícius Silva Guido
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Small interfering RNAs (siRNAs) represent a promising approach for gene therapy due to their ability to specifically and efficiently silence target genes. However, challenges such as enzymatic degradation, immune activation, and difficulties in crossing biological barriers underscore the need for effective delivery systems with clinical viability. This project aims to develop human serum albumin-based nanoparticles (HSA-PNPs) for siRNA encapsulation and delivery to address these challenges. HSA-PNPs will be designed to maximize therapeutic efficiency by incorporating advanced strategies that combine pH-induced cationization during endosomal acidification and controlled siRNA release mediated by the reductive cytosolic environment. The biocompatibility of the formulations will be ensured through rigorous testing in human whole blood. This aspect, often overlooked, is crucial to prevent adverse interactions, as preparation methods can induce chemical and structural alterations in albumin. This study will contribute to advancing the use of protein-based nanoparticles in siRNA-based gene therapy while deepening our understanding of the molecular mechanisms governing the efficacy and safety of these delivery systems.