Albumin Nanoparticles in Cancer Nanomedicine: Optimizing Biocompatibility, Cellular Delivery, and Therapeutic Efficacy

• Grant number: 25/01716-7
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2025
• End date: August 31, 2028
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Alioscka Augusto Sousa
• Grantee: Alioscka Augusto Sousa
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Cancer remains one of the leading causes of mortality worldwide, and its effective treatment continues to be a significant challenge. Over the past decades, nanomedicine has emerged as a valuable addition to the therapeutic arsenal in the fight against cancer. Among the available approaches, albumin nanoparticles (HSA-PNPs) stand out due to their simplicity of preparation, versatility in applications, and high biocompatibility. However, the consolidation of HSA-PNPs in cancer nanomedicine still requires strategic advancements in key areas. In this context, the present project aims to develop novel HSA-PNPs as carriers for chemotherapeutics (SN-38) and siRNAs in targeted cancer therapies. The study addresses critical challenges in the field of HSA-PNPs, encompassing particle synthesis, endocytosis, optimization of siRNA delivery, and improvement of blood compatibility. The project is structured into three main subprojects: (i) Development of biologically responsive HSA-PNPs designed to induce cationization and particle disintegration, optimizing efficient siRNA delivery to the cytosol and enhancing therapeutic efficacy; (ii) Investigation of the interactions between HSA-PNPs and SPARC protein, which is widely expressed in various tumors, aiming to leverage these interactions to improve cellular uptake and therapeutic performance; and (iii) Evaluation of the blood compatibility of HSA-PNPs using an ex vivo model simulating whole human blood circulation, examining the impacts of preparation methods and albumin conformational changes on biocompatibility. (AU)