The most critical problem in the treatment of neurodegenerative diseases is brain neuronal protection, which can be overcome by clearing pathological substances and regulating the immune environment. In the above treatment strategies, the traditional poor drug delivery problem is inevitable. Here, researchers show an engineering core-shell hybrid system named rabies virus glycoprotein (RVG) peptide–modified exosome (EXO) curcumin/phenylboronic acid-poly(2-(dimethylamino)ethyl acrylate) nanoparticle/small interfering RNA targeting SNCA(REXO-C/ANP/S). It is a nanoscavenger for clearing α-synuclein aggregates and reducing their cytotoxicity in Parkinson’s disease neurons. The motor behavior of Parkinson’s disease mice is substantially improved after REXO-C/ANP/S treatment. In particular, the researchers demonstrate that REXO-C/ANP/S is also a nanoscavenger for clearing immune activation due to its natural immature dendritic cell EXO coating. Our findings show that REXO-C/ANP/S may serve as a platform for neurodegenerative diseases treatment.
(A) Scheme of REXO-C/ANP/S preparation. (B) Zeta potential and diameters of NPs under different REXO:C/ANP/S ratios. (C) TEM images of NPs under different REXO:C/ANP/S ratios (I, low REXO:C/ANP/S ratio; II, intermediate; and III, high REXO:C/ANP/S ratio). Scale bars, 100 nm. (D) Comparison in zeta potential and diameters of REXO, C/ANP/S, and REXO/ANP/S. (E) Chitosan microsphere with REXO-C/ANP/S absorption. Cy5-siSNCA, blue; curcumin, green; and DiI-labeled exosome, red. (F) Western blot band of TSG101 and CD9 of EXO and REXO-C/ANP/S.