Near-Infrared Radiation-Assisted Drug Delivery Nanoplatform to Realize Blood–Brain Barrier Crossing and Protection for Parkinsonian Therapy

Abstract

Mitochondrial dysfunction, which is directly involved in Parkinson’s disease (PD), is characterized by the production of reactive oxygen species (ROS) and aberrant energy metabolism. Thus, regulating mitochondrial function might be an effective strategy to treat PD. However, the blood–brain barrier (BBB) presents a significant challenge for the intracerebral delivery of drugs. Here, we synthesized a zeolitic imidazolate framework 8-coated Prussian blue nanocomposite (ZIF-8@PB), which was encapsulated with quercetin (QCT), a natural antioxidant, to treat PD. ZIF-8@PB-QCT exhibited superior near-infrared radiation (NIR) response and penetrated through the BBB to the site of mitochondrial damage guided by the photothermal effect. In the mice model of PD, the QCT released from ZIF-8@PB-QCT significantly increased the adenosine triphosphate levels, reduced the oxidative stress levels, and reversed dopaminergic neuronal damage as well as PD-related behavioral deficits without any damage to the normal tissues. Furthermore, we explored the underlying neuroprotective mechanism of ZIF-8@PB-QCT that was mediated by activating the PI3K/Akt signaling pathway. Thus, combined with noninvasive NIR radiation, the biocompatible ZIF-8@PB-QCT nanocomposite could be used to treat neurodegenerative diseases.

The Effect of Oxidative Stress and Memantine-Incorporated Reactive Oxygen Species-Sensitive Nanoparticles on the Expression of N-Methyl-d-aspartate Receptor Subunit 1 in Brain Cancer Cells for Alzheimer’s Disease Application

“…The physiological state of the brain is quite different to that of other organs because the BBB is a primary obstacle for drug delivery to the brain [25,26]. For this reason, various delivery platforms have been investigated to improve the penetration and/or transport of bioactive agents [26][27][28][29][30][31][32][33][34][35][36][41][42][43][44][45][46][47]. For example, surfactants such as polysorbate 80 have been used to allow nanoparticles or drug carriers to penetrate the BBB [41][42][43][44][45][46].…”

“…Monoclonal antibodies such as OX-26 can be used to decorate nanoparticles for the brain delivery of bioactive agents [44]. Liu et al reported that zeolite imidazolate framework 8-based nanocomposites delivered quercetin to the brain, reduced oxidative stress and reversed dopaminergic neuronal damage [34]. They argued that nanocomposites can be used for neurodegenerative diseases without any damage to the normal tissues according to the results found in a mouse model.…”

“…Nano-dimensional carriers are characterized by small particle sizes, diversity of customized form, ease of lipophilic drug encapsulation, increased half lives in the body, and targeting of the drug to specific sites of action [31]. In particular, nanoparticles are considered as a promising device to treat neuro-degenerative disease through enhanced drug delivery across the BBB [32][33][34][35]. Liu et al reported that zeolitic imidazolate framework 8-coated Prussian blue nanocomposite could penetrate the BBB and then released quercetin [34].…”

“…In particular, nanoparticles are considered as a promising device to treat neuro-degenerative disease through enhanced drug delivery across the BBB [32][33][34][35]. Liu et al reported that zeolitic imidazolate framework 8-coated Prussian blue nanocomposite could penetrate the BBB and then released quercetin [34]. They showed that nanocomposites significantly increased the level of adenosine phosphate, reduced the oxidative stress and reversed dopaminergic neuronal damage.…”

Natural Products and Nanotechnology Against Coronavirus Disease 2019

“…Nanotechnology has developed rapidly in recent years, and natural products, including herbal therapy based on nanotechnology, are becoming increasingly popular and are showing very broad application prospects ( Liu et al, 2021 ; Zhang et al, 2021 ; Zhu et al, 2021 ). Nanotechnology usually refers to the use of nanomaterials with sizes between 1 and 100 nm, which can be classified as organic and inorganic nanoparticles.…”