Synthesis, Characterization, and Neuroprotective Activity of Flavonoid-Complexed Carbon Dots via Microfluidic Route in Alzheimer's Disease Neurospheroids

• Grant number: 25/05572-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2025
• End date: October 31, 2028
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Lucimara Gaziola de la Torre
• Grantee: Viviane Lucia Beraldo de Araújo
• Host Institution: Faculdade de Engenharia Química (FEQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 18/12605-8 - Development of brain-on-a-chip microplataforms for in vitro modeling of the central nervous system, AP.TEM

Abstract

This research project aims to produce and characterize carbon dots derived from passion fruit peel (CDCM) as a carbonaceous precursor, to complex them with flavonoids, and evaluate their neuroprotective activity in a three-dimensional model of Alzheimer's disease (AD). AD is a neurodegenerative disorder accounted for 50-75% of dementia cases worldwide, with a multifactorial cause and unknown cure. Studies have demonstrated that flavonoids possess antioxidant properties in vitro and ex vivo, indicating improved survival of dopaminergic neurons after neurotoxin injection in mice. This neuroprotective potential has shown promise for application in other translational models of neurodegeneration and brain aging. With this in mind, the first phase of the study will involve the production and physicochemical characterization of CDCM. After this, their complexation with flavonoids will be carried out to maintain the stability of these bioactive molecules, enhance their bioavailability, and enable targeted delivery across the blood-brain barrier. In the second phase, neurospheroids will be produced in a microfluidic device as 3D models to simulate in vivo conditions for AD modeling and bioactive molecule screening, particularly to understand the neuroprotective effects of flavonoids. The neurospheroids will be characterized using immunofluorescence to assess specific tissue markers, and their morphology will be analyzed through reinforcement learning-a form of artificial intelligence (AI) that will allow for determining the parameters of cellular dynamics within the spheroids. Finally, the neuroprotective evaluation will be conducted by assessing the antioxidant and anti-inflammatory capacity of the formulation and its ability to reduce beta-amyloid aggregates, which are present in AD, using instrumental analysis techniques. Theproduced complex will also be tested in a validated model of healthy and AD-affected cerebral vasculature using a microfluidic device during an international research internship supervised by Prof. Dr. Peter Searson at the Department of Materials Science and Engineering, Johns Hopkins University, United Statesof America. This study is expected to yield promising results in the search for new neuroprotective compounds that mitigate physiological changes associated with AD, highlighting the importance of multidisciplinarity by integrating instrumental analysis techniques, microfluidic 3D cell culture systems, and nanostructured systems modeled with AI. (AU)