Fucoidan-derived carbon dots as nanopenetrants of blood-brain barrier for Parkinson’s disease treatment

Abstract

Parkinson’s Disease (PD) stands as a prevalent neurodegenerative disorder. However, current pharmacotherapies for PD face challenges due to inadequate penetration through the blood–brain barrier (BBB), posing limitations on their therapeutic efficacy. Considering the potential of negatively charged carbon dots (CDs) in retaining functional groups from precursor molecules and vertically crossing the BBB, this study focuses on the utilization of fucoidan (FD), a promising pharmaceutical candidate with neuroprotective effects on dopamine-active neurons, for the development of negatively charged CDs through a one-step hydrothermal method, aiming to achieve efficient BBB penetration for PD treatment. The obtained fucoidan-derived carbon dots (FDCDs) exhibit the fundamental characteristics of CDs, such as nanostructure particles with an average diameter of less than 10 nm and significant photoluminescence ability. They also retain the abundant functional groups of SO₄^2- from FD, resulting in a negatively charged surface. In vitro cell experiments were conducted to validate the ability of FDCDs to mitigate 1-Methyl-4-phenylpyridinium ion (MPP⁺)-induced damage in PC12 cells via anti-inflammatory pathway, antioxidant capacity, and anti-apoptotic effect. After confirming the ability of FDCDs to traverse the BBB using 3D small animal imaging, the intravenous administration of FDCDs via tail injection was observed to successfully restore the motor function in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice. Notably, no apparent biotoxic response was observed, highlighting the promising potential of FDCDs for effective PD therapy.