“Cell-addictive” dual-target traceable nanodrug for Parkinson's disease treatment via flotillins pathway

α-synclein (αS) aggregation is a representative molecular feature of the pathogenesis of Parkinson's disease (PD).Epigallocatechin gallate (EGCG) can prevent αS aggregation in vitro.However, the in vivo effects of PD treatment are poor due to the obstacles of EGCG accumulation in dopaminergic neurons, such as the blood brain barrier and high binding affinities between EGCG and membrane proteins.Therefore, the key to PD treatment lies in visual examination of EGCG accumulation in dopaminergic neurons.Methods: DSPE-PEG-B6, DSPE-PEG-MA, DSPE-PEG-phenylboronic acid, and superparamagnetic iron oxide nanocubes were self-assembled into tracing nanoparticles (NPs).EGCG was then conjugated on the surface of the NPs through the formation of boronate ester bonds to form a "cell-addictive" dual-target traceable nanodrug (B6ME-NPs).B6ME-NPs were then used for PD treatment via intravenous injection.Results: After treatment with B6ME-NPs, the PD-like characteristics was alleviated significantly.First, the amount of EGCG accumulation in PD lesions was markedly enhanced and traced via magnetic resonance imaging.Further, αS aggregation was greatly inhibited.Finally, the dopaminergic neurons were considerably increased.Conclusion: Due to their low price, simple preparation, safety, and excellent therapeutic effect on PD, B6ME-NPs are expected to have potential application in PD treatment.