Recent Developments of Nanotechnology for Alzheimer’s Disease Diagnosis and Therapy
Xinyu Dai1, Yuntao Li1* and Yuejiao Zhong2
1 Department of Neurology, Second Affiliated Hospital of Nanjing Medical University, China
2Department of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, China
Submission: August 15, 2018; Published: October 25, 2018
*Corresponding author: Yuntao Li, Department of General Practice, Second Affiliated Hospital of Nanjing Medical University, No 121 Jiangjiayuan Road, Nanjing 210011, China.
How to cite this article: Xinyu D, Yuntao L, Yuejiao Z. Recent Developments of Nanotechnology for Alzheimer’s Disease Diagnosis and Therapy. Glob J
Nano. 2018; 4(4): 555644. DOI: 10.19080/GJN.2018.04.555644
Alzheimer’s disease (AD) is a common neurodegenerative disease-causing memory loss and deterioration of cognitive function. In addition, it displays other neurological symptoms such as delusions, deficiency in language, learning, and abstract thinking. The symptoms of the disease progress gradually, which can eventually lead to incapacitation of the individuals functioning. AD will have enormous social and economic impacts in the coming decades. Therefore, strategies for early detection and treatment of AD has become one of the most challenging in modern medicine. Drug and imaging agent’s delivery to the brain remains the main problems for the diagnosis and treatment of AD because of the protection of blood-brain barrier (BBB), however, nanoparticles can help overcome the limitations of BBB. In this article, we have explored latest developments in nanotechnology-based AD diagnosis and therapy
Generally, nanotechnology refers to the measurement and modeling of substances in a nanoscale manner, which can be applied to engineering and technology by manipulating or modifying material materials to give them new properties. In current medical research, new diagnostic and therapeutic tools were developed combined with nanotechnology, which are beneficial to the specific transport and absorption of drugs and contrast agents to the brain and promote the regeneration of damaged neurons to limit or reverse neurological disorder. New Nano pharmaceutical technology that combines polymer nanoparticles, liposomes, micelles, dendrimers, and nanogels could enhance passage of drugs and small molecules a crossing the BBB.
AD as a common neurological disease there were 46.8 million people worldwide living with dementia in 2015 and this number will gradually increase to 131.5 million in 2050 . There were three mutant genes have been reported to cause AD, including the gene encoding the amyloid precursor protein (APP) on chromosome 21, and the gene encoding presenilin 1 (PS1) on chromosome 14 and the gene encoding presenilin
2 (PS2) on the chromosome 1. These mutations can cause the amyloid-β protein (Aβ) to form senile plaques extracellularly, while the microtubule-associated protein tau (Tau) is hyperphosphorylated to form neurofibrillary tangles. These changes throughout the brain leads to extensive cortical damage and early loss of basal forebrain cholinergic neurons . Among them, Aβ has become the main focus of neurodegenerative research and many current treatments are targeted to the production, fibrosis and clearance of Aβ. Although the treatment strategy is advanced, there is no obvious clinical benefit, and currently approved neurotransmitter-modulating drugs can only improve symptoms.
The pathogenesis of AD is multifactorial, and it is not easy to detect behavioral and memory changes caused by disease at an early stage. So, it is important to explore early markers to predict the onset of disease. As a biomarker, current research indicates that Aβ deposition is the first pathogenic event that occurs before clinical symptoms appear, and neurofibrillary tangles promote its development and exhibit detectable clinical symptoms [3,4]. Therefore, it can be speculated that Aβ and Tau proteins have been concentrated in cerebral spinal fluid (CSF) before clinical onset. In addition to exploring biomarkers, because the net charge of Aβ is negative, multivalent cations
can bind Aβ and accelerate the process of aggregation and
fibrillation, thus monitoring plasma multivalent cations (eg zinc,
copper, iron, etc.) are expected in the early detection of AD .
Since neuro invasiveness and degenerative changes have
begun before the onset of AD symptoms, early diagnosis is the
key to effective treatment of AD. Most studies focus on magnetic
resonance imaging (MRI) using contrast-doped NPs or labeling
NPs with fluorescent probes to detect and identify amyloid
Magnetic iron oxide NPs have gained wide attention due to
their large surface area, good magnetic properties, low toxicity,
and good biocompatibility and degradability. For example,
Cheng et al.  synthesized superparamagnetic iron oxide
nanoparticles (SPIONs) connected with curcumin which coated
with polyethyleneglycol (PEG)-lactic acid (PLA). The material is
non-cytotoxic and has the ability to detect amyloid plaques in
the brain of Tg2576 mice with AD  (Figure 1). Both top and
bottom images were viewed by confocal microscopy. Top images
were bright view and bottom images were fluorescence signal
from stained chemical (from left to right stain by thioflavin T,
curcumin or curcumin-MNPs) .
Lai et al exposed these sites to an aqueous solution of
chloroauric acid to form a gold salt by targeting the site of
infection . These salts are assembled into gold nanoclusters
(AuNC) for fluorescence imaging. Within a few hours after the
injection of chloroauric acid by the tail vein of AD mice, there
was a clear fluorescent label around the affected part of the
brain, whereas the control mice did not show any fluorescent
area after intravenous injection of chloroauric acid for 24 hr
BBB is the primary barrier to the delivery of therapeutic
drugs to the brain. Some treatments have forced them to open
by causing structural damage to the BBB, at which point the
BBB has lost its selectivity for drug passage. The carrier system
combined with nanotechnology is the most promising treatment
strategy for delivering drugs to the brain through the BBB. The
current common delivery systems are shown in (Table 1) .
Cholinergic anti-inflammatory effects play an important
role in preventing the development of learning and memory
disorders in AD patients, so acetylcholinesterase (AChE)
inhibitors can be used for symptomatic treatment of AD. As an
inhibitor of AchE and butyrylcholinesterase, rivastigmine was
approved by the FDA in 2000 for the treatment of AD. Studies
have shown that coating the drug in nanoparticles enhances the
targeted delivery of rivastigmine and reduces the side effects of
free drug administration [10-13].
Curcumin can enhance mitochondrial function and may
be suitable for preventing AD. However, the bioavailability
of curcumin is low. Some studies have suggested that the
bioavailability of curcumin micelles is higher than that of natural curcumin, and the encapsulation of nanoparticles can increase
the solubility of curcumin, prolong the circulation time in the
body, and improve the Targeted release within brain [14-17].
There is also evidence that metals have the effect of damaging
neurons. The level of metal ions can be reduced by the use of
chelating agents that target the interaction between Aβ and
metal ions in the brain of AD patients [18,19].
It is well known that NPs will be immediately covered by
proteins to form protein crowns after coming into the biological
environment , and the effect of protein crowns on Aβ fibrosis
should be assessed. Different diseases may also alter the fate
of NPs in the body, so NPs may also have different therapeutic
effects or toxic effects after entering different patients. These
studies suggest that in the future research of Nanotechnology,
a variety of hidden factors in the nanobio interface should be
considered. The potential toxicity of NPs is another important
issue, and there are few reports around long-term toxicity after
NPs use. In order to solve these problems, it has been expected
to develop multifunctional NPs with multiple therapeutic
capabilities, for example, comprehensive control of Tau protein
phosphorylation, inflammatory response, redox reaction and
improvement of mitochondrial.
Research undertaken so far to transport drugs via
nanocarriers across the BBB, while considerable, has certainly
not enough and has not met expectations , so there is an
urgent need to re-examine current research ideas and methods
to improve or find new ways.
Since the discovery of central nervous system degenerative
diseases, its diagnosis and treatment have become a huge
medical challenge. In addition to research in the biological field,
the combination with other fields, especially the integration
of nanotechnology, has showed us a promising way. Current
research indicates that the surface of NPs can be modified
by covalent and non-covalent connection, giving it additional
stability and drug affinity. In the future, we hope to see
nanotechnology-based drug delivery systems can effectively treat
more Invasive neurological disease or drug resistant disease.
In addition, the functionalization of NPs and the combination
of drugs indicate more possibilities, not only for drug system
construction, but also for gene and protein delivery. Some
nanoparticles also have special magnetic and optical properties,
etc., giving them magnetic targeting and photothermal effects.
With the advancement of nanotechnology, NPs will appear more
in biomedical application.
This work was supported by the National Natural Science
Foundation of China (grant number: 81301313; 81600159), the
Natural Science Foundation of Jiangsu Province (grant number:
BK20131015; BK20141015), Jiangsu Provincial College
Students’ Practical Innovation Training Program (grant number:
201410312015Z), and Nanjing Developing Project of Medical
Science (grant number: YKK13174).