Targeting modulation of intestinal flora through oral route by an antimicrobial nucleic acid-loaded exosome-like nanovesicles to improve Parkinson’s disease

Parkinson’s disease(PD)is one of the most prevalent neurodegenerative diseases.It is usually accompanied by motor and non-motor symptoms that seriously threaten the health and the quality of life.Novel medications are urgently needed because current pharmaceuticals can relieve symptoms but cannot stop disease progression.The microbiota-gut-brain axis(MGBA)is closely associated with the occurrence and development of PD and is an effective therapeutic target.Tetrahedral framework nucleic acids(tFNAs)can modulate the microbiome and immune regulation.However,such nucleic acid nanostructures are very sensitive to acids which hinder this promising approach.Therefore,we prepared exosome-like nanovesicles(Exo@tac)from ginger that are acid resistant and equipped with tFNAs modified by antimicrobial peptides(AMP).We verified that Exo@tac regulates intestinal bacteria associated with the microbial-gut-brain axis in vitro and significantly improves PD symptoms in vivo when administered orally.Microbiota profiling confirmed that Exo@tac normalizes the intestinal flora composition of mouse models of PD.Our findings present a novel strategy for the development of PD drugs and the innovative delivery of nucleic acid nanomedicines.

Isolation of cabbage exosome-like nanovesicles and investigation of their biological activities in human cells

There are extensive studies on the applications of extracellular vesicles(EVs)produced in cell culture for therapeutic drug development.However,large quantities of EVs are needed for in vivo applications,which requires high production costs and time.Thus,the development of new EV sources is essential to facilitate their use.Accordingly,plant-derived exosome-like nanovesicles are an emerging alternative for culture-derived EVs.Until now,however,few studies have explored their biological functions and uses.Therefore,it is necessary to elucidate biological activities of plant-derived exosome-like nanovesicles and harness vesicles for biomedical applications.Herein,cabbage and red cabbage were used as nanovesicle sources owing to their easy cultivation.First,an efficient method for nanovesicle isolation from cabbage(Cabex)and red cabbage(Rabex)was developed.Furthermore,isolated nanovesicles were characterized,and their biological functions were assessed.Both Cabex and Rabex promoted mammalian cell proliferation and,interestingly,suppressed inflammation in immune cells and apoptosis in human keratinocytes and fibroblasts.Finally,therapeutic drugs were encapsulated in Cabex or Rabex and successfully delivered to human cells,demonstrating the potential of these vesicles as alternative drug delivery vehicles.Overall,the current results provide strong evidence for the wide application of Cabex and Rabex as novel therapeutic biomaterials.