Nanotechnology-empowered therapeutics targeting neurodegenerative diseases

Abstract

Neurodegenerative diseases are posing pressing health issues due to the high prevalence among aging populations in the 21st century. They are evidenced by the progressive loss of neuronal function, often associated with neuronal necrosis and many related devastating complications. Nevertheless, effective therapeutical strategies to treat neurodegenerative diseases remain a tremendous challenge due to the multisystemic nature and limited drug delivery to the central nervous system. As a result, there is a pressing need to develop effective alternative therapeutics to manage the progression of neurodegenerative diseases. By utilizing the functional reconstructive materials and technologies with specific targeting ability at the nanoscale level, nanotechnology-empowered medicines can transform the therapeutic paradigms of neurodegenerative diseases with minimal systemic side effects. This review outlines the current applications and progresses of the nanotechnology-enabled drug delivery systems to enhance the therapeutic efficacy in treating neurodegenerative diseases. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Keywords: blood brain barrier; central nervous system; drug delivery; nanotechnology; neurodegenerative diseases.

Figure 1.

The most common neurodegenerative diseases and corresponding types of affected neurons.

Figure 2.

Five main modes of drug traverse the BBB.

Figure 3.

The mechanism of curcumin encapsulated PLGA nanoparticles (Cur-PLGA-NPs) inducing NSC proliferation and neuronal differentiation. Reproduced with permission from(Tiwari et al., 2014).

Figure 4.

Schematic illustration of delivery and potential therapeutic mechanism of PR-EXO/PP@Cur nanocarriers. Reproduced with permission from(Peng et al., 2022).

Figure 5.

Effect of C-Mn3O4 NPs for anxiety and depression-like behavior test. OFT. a) Representative tracks inside the open field. b) Time spent at the center. c) Total distance moved. d) Average speed. EPM test. e) Trace of movement in EPM. f) Time spent in open arm. g) Distance moved in open arm. h) Total distance moved. i) Light preference test. Time spent in light zone and transitions into light zone. FST. j) Total immobility time, k) total climbing time, l) total swimming time, and m) latency to first immobility event. n) SPT. Data are expressed as Mean ± SD. N = 6. Statistical significance versus control group (***p < 0.001; **p < 0.01; *p < 0.05). Reproduced with permission from(Adhikari et al., 2021).

Figure 6.

Edaravone agonistic micelles specifically activated A₂AR over-expressed in the capillaries of brain ischemia, increased BBB penetration by temporarily opening para-endothelial tight junctions (TJs), entered brain ischemia by crossing the compromised TJs, released the encapsulated edaravone, and sustainably eradicated ROS excreted by brain-derived cells (microglia, astrocytes and endothelium) as well as infiltrated inflammatory cells (macrophages and neutrophils). Reproduced with permission from(Jin et al., 2017).