Brain-Targeted Biomimetic Nanodecoys with Neuroprotective Effects for Precise Therapy of Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the gradual loss of dopaminergic neurons in the substantia nigra and the accumulation of α-synuclein aggregates called Lewy bodies. Here, nanodecoys were designed from a rabies virus polypeptide with a 29 amino acid (RVG29)-modified red blood cell membrane (RBCm) to encapsulate curcumin nanocrystals (Cur-NCs), which could effectively protect dopaminergic neurons. The RVG29-RBCm/Cur-NCs nanodecoys effectively escaped from reticuloendothelial system (RES) uptake, enabled prolonged blood circulation, and enhanced blood–brain barrier (BBB) crossing after systemic administration. Cur-NCs loaded inside the nanodecoys exhibited the recovery of dopamine levels, inhibition of α-synuclein aggregation, and reversal of mitochondrial dysfunction in PD mice. These findings indicate the promising potential of biomimetic nanodecoys in treating PD and other neurodegenerative diseases.

Microfluidic Synthesis of the Tumor Microenvironment-Responsive Nanosystem for Type-I Photodynamic Therapy

“…Microfluidic technology, as one of the most promising technologies, can well integrate the nanoparticle synthesis platform into a small glass chip, rendering the synthesis of nanoparticles more controllable [ 26 ]. In general, the small size of nanoparticles, their large specific surface area, and their quantum size effect endow them with special properties lacking in conventional materials [ 27 ]. The mechanism for its formation is based on the classical nucleation theory; that is, the raw materials accumulate rapidly in the solution to form a specific supersaturated state, which overcomes the energy barrier for nucleation and finally leads to explosive nucleation [ 11 , 28 ].…”

The Landscape of Biomimetic Nanovesicles in Brain Diseases

“…Modification of peptides (such as neuroinvasive peptides (e.g., RVG) and brain targeting peptides (e.g., angiopoietin 2 (ANG2)) is the common chemical engineering method for BNVs. For example, rabies‐virus‐polypeptide‐RVG29‐modified erythrocyte membrane possessed higher endothelial cell uptake efficiency in a bEnd.3‐derived BBB model in vitro, [ 60 ] as RVG could specifically identify acetylcholine receptors expressed on neurons and BBB for drug delivery in PD. [ 85 ] ANG2 can bind to low‐density lipoprotein receptor‐related protein 1 expressed in brain endothelial cells and neuronal cells to enhance brain parenchyma penetration and brain targeting.…”

Parkinson's Disease: Current Status, Diagnosis, and Treatment Using Nanomedicines

“…[76,81] The therapeutic efficacy of an anti-Parkinson's disease drug is significantly increased by membrane-coated nanoparticles due to their benefits in homologous targeting, extended circulation, and the inhibition of immunological reactions. [76,82] For example, Liu et al illustrated that the rabies virus polypeptide RVG29, which has 29 amino acids and can specifically bind to acetylcholine receptors (nAChRs) expressed in both the BBB and neural cells. This modified rabies virus polypeptide, RVG29, was combined with the natural RBCm to develop it as a drug delivery carrier for the brain.…”

“…As a result, it demonstrates effective drug delivery to the brain for the treatment of PD as well as inhibition of abnormal α‐syn aggregation ( Figure ). [ 82 ] Further research is required for designing and developing cell membrane‐coated biomimetic nanoparticles for targeted delivery to the brain, as well as for advanced experiments required for safe, effective therapies for clinical translation. Furthermore, encapsulation or conjugation of cell membrane‐coated biomimetic nanoparticles with drug molecules holds great promise for effective Parkinson's disease therapy.…”

“…(J) Fluorescence intensity measurement is the main. Reproduced with permission [82]. Copyright 2022, ACS.…”