CAR-NK cell membrane as a coating for antifungal-loaded polymeric nanoparticles for targeted therapy against invasive candidiasis

• Grant number: 24/18033-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2025
• End date: August 31, 2028
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Thiago Aparecido da Silva
• Grantee: Gabriela Yamazaki de Campos
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Invasive candidiasis is a severe fungal infection caused by species of the Candida genus, such as Candida albicans, Candida glabrata, Candida tropicalis, and Candida auris. It is more prevalent in immunocompromised patients and associated with high mortality rates. Treatment with antifungals, such as azoles, polyenes, and echinocandins, can lead to severe adverse effects and face resistance, compromising therapeutic efficacy. In this context, the development of new therapeutic strategies that integrate immunotherapy and nanotechnology represents a promising and innovative solution for this neglected disease. The use of nanoparticles (NPs) for controlled and targeted antifungal delivery is expanding but still faces challenges for safe clinical application, such as opsonization, protein corona formation, and reduced circulation time in the body. Cell membrane-coated NPs, offering biomimetic properties, emerge as a promising alternative to overcome these limitations. This project proposes combining immunotherapy advances with the development of polymeric NPs containing antifungal drugs, coated with membranes from natural killer (NK) cells expressing a chimeric antigen receptor (CAR) highly specific to different Candida species. The NK-92 cell line will be modified with scFvk3-1-CAR, specific for Candida spp, and the membranes will be isolated after obtaining and confirming the modified cells by flow cytometry. Simultaneously, polymeric PLGA-NPs containing caspofungin will be synthesized by double emulsification and coated with CAR-NK membranes, followed by several characterization techniques. The antifungal effect of CAR-NK-NPs will be evaluated in vitro and in vivo. This innovative approach offers a biomimetic system capable of efficiently targeting antifungals to Candida spp. infection sites, reducing toxicity and other adverse effects. (AU)