Nanotechnology-Inspired Extracellular Vesicles Theranostics for Diagnosis and Therapy of Central Nervous System Diseases

Abstract

Shuttling various bioactive substances across the blood−brain barrier (BBB) bidirectionally, extracellular vesicles (EVs) have been opening new frontiers for the diagnosis and therapy of central nervous system (CNS) diseases. However, clinical translation of EV-based theranostics remains challenging due to difficulties in effective EV engineering for superior imaging/ therapeutic potential, ultrasensitive EV detection for small sample volume, as well as scale-up and standardized EV production. In the past decade, continuous advancement in nanotechnology provided extensive concepts and strategies for EV engineering and analysis, which inspired the application of EVs for CNS diseases. Here we will review the existing types of EV−nanomaterial hybrid systems with improved diagnostic and therapeutic efficacy for CNS diseases. A summary of recent progress in the incorporation of nanomaterials and nanostructures in EV production, separation, and analysis will also be provided. Moreover, the convergence between nanotechnology and microfluidics for integrated EV engineering and liquid biopsy of CNS diseases will be discussed.

Nano-Brush Structure for Rapid Label-Free Differentiation of Alzheimer’s Disease Stages and Direct Capture of Neuron-Derived Exosomes from Human Blood Plasma

“…Small protrusions on the sensing substrate could lead to substantial variations in the substrate’s interaction with the target analytes based on the extended Derjauin–Landau–Verwey–Overbeek (DLVO) theory . In terms of the ratio of particle size to asperity size on the sensing substrate in the extended DLVO theory, the 400 nm surface roughness of the modified nano-brush sensing substrate may provide adequate interfacial interactions with target analytes, such as H + and NDE (30–150 nm), , enhancing the sensing performance. Figure D–F shows the topographical morphology of ITO/USNWs, APTMS/ITO/USNWs, and NFLAb/APTMS/ITO/USNWs, respectively, using AFM.…”

“…NFL levels have been proposed to predict disease progression in the early presymptomatic stages of familial AD and have also been associated with disease severity and prognosis in frontotemporal dementia. 3,5,8 On the other hand, exosomes, nano-sized extracellular vesicles (EVs) (30−150 nm) found in biofluids, carry important biomolecules from their cell of origin. 8−10 Exosomes have been extensively studied for their potential in diagnosing and predicting various dementia diseases, including AD, 4,9,11−14 Parkinson's disease (PD), 15 and mental disorders.…”

“…Neurofilament light chain (NFL) levels and neuron-derived exosomes (NDEs) in the central nervous system and human blood plasma/serum are promising biomarkers for early stages of AD. NFL levels have been proposed to predict disease progression in the early presymptomatic stages of familial AD and have also been associated with disease severity and prognosis in frontotemporal dementia. ,, On the other hand, exosomes, nano-sized extracellular vesicles (EVs) (30–150 nm) found in biofluids, carry important biomolecules from their cell of origin. − Exosomes have been extensively studied for their potential in diagnosing and predicting various dementia diseases, including AD, ,,− Parkinson’s disease (PD), and mental disorders. − Specialized synaptic proteins in NDEs ,, and Aβ-NDEs ,, have been applied to predict AD development before clinical symptoms appear. These studies suggest that specific exosomes released by neurons can cross the blood–brain barrier and serve as accessible diagnostic markers for neural dysfunction and diseases.…”

Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions

“…Nanotheranostics represents a cutting-edge convergence of nanotechnology, diagnostics, and therapeutics [ 199 – 201 ]. The nanotheranostic potential of EVs in CNS diseases is an exciting and rapidly developing area of research that explores the use of EVs for both therapeutic and diagnostic purposes in the CNS [ 49 – 51 ]. EVs present a natural and versatile option for this purpose.…”

Tissue Engineering in Neuroscience: Applications and Perspectives

“…To address the issues of nerve regeneration, a growing number of techniques for repairing and treating nerve damage are being employed [ 10 , 11 ]. Surgery, drugs, cell therapy, exosomes, and tissue engineering (TE) scaffolds, are the most frequently employed treatment methods [ 12 – 15 ]. Among them, the rise and development of TE and regenerative medicine have brought a new approach for repairing and regenerating the damaged tissues and organs, thus transcending conventional treatment’s limitations.…”