Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 May 26:12:683935.
doi: 10.3389/fphar.2021.683935. eCollection 2021.

Nanoparticles: A Hope for the Treatment of Inflammation in CNS

Feng-Dan Zhu  1 , Yu-Jiao Hu  1   2 , Lu Yu  1 , Xiao-Gang Zhou  1 , Jian-Ming Wu  1 , Yong Tang  1 , Da-Lian Qin  1 , Qing-Ze Fan  1   3 , An-Guo Wu  1   3
Affiliations
Review

Nanoparticles: A Hope for the Treatment of Inflammation in CNS

Feng-Dan Zhu et al. Front Pharmacol. .

Abstract

Neuroinflammation, an inflammatory response within the central nervous system (CNS), is a main hallmark of common neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), among others. The over-activated microglia release pro-inflammatory cytokines, which induces neuronal death and accelerates neurodegeneration. Therefore, inhibition of microglia over-activation and microglia-mediated neuroinflammation has been a promising strategy for the treatment of neurodegenerative diseases. Many drugs have shown promising therapeutic effects on microglia and inflammation. However, the blood-brain barrier (BBB)-a natural barrier preventing brain tissue from contact with harmful plasma components-seriously hinders drug delivery to the microglial cells in CNS. As an emerging useful therapeutic tool in CNS-related diseases, nanoparticles (NPs) have been widely applied in biomedical fields for use in diagnosis, biosensing and drug delivery. Recently, many NPs have been reported to be useful vehicles for anti-inflammatory drugs across the BBB to inhibit the over-activation of microglia and neuroinflammation. Therefore, NPs with good biodegradability and biocompatibility have the potential to be developed as an effective and minimally invasive carrier to help other drugs cross the BBB or as a therapeutic agent for the treatment of neuroinflammation-mediated neurodegenerative diseases. In this review, we summarized various nanoparticles applied in CNS, and their mechanisms and effects in the modulation of inflammation responses in neurodegenerative diseases, providing insights and suggestions for the use of NPs in the treatment of neuroinflammation-related neurodegenerative diseases.

Keywords: blood-brain barrier; central neural system; nanoparticles; neurodegenerative diseases; neuroinflammation.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The key role of neuroinflammation in neurodegenerative diseases. The resting microglia (M0) are over-activated by PAMPs/DAMPs into a pro-inflammatory state (M1), which leads to the generation of pro-inflammatory cytokines. The treatment of anti-inflammatory drugs can inhibit the over-activation of microglia and promote the microglia into an anti-inflammatory state to maintain the balance of M1/M2 type microglia.
FIGURE 2
FIGURE 2
The classification of NPs and the role of NPs in CNS-related diseases. NPs are mainly classified into three groups: organic, carbon-based, and inorganic NPs. In general, these NPs are administrated via the gastrointestinal system, respiratory tract, nasal cavity, and skin, etc. They cross the BBB into the target brain cells including neurons, microglia and astrocyte to exert protective and degenerative effects.
FIGURE 3
FIGURE 3
NPs serve as a drug delivery system in neuroinflammation-mediated CNS-related diseases. NPs delivery systems help drugs cross the BBB to inhibit over-activated microglia and its resultant neuroinflammatory response, which promotes the transformation of M1-type microglia into M2-type microglia and improves neuronal viability.
FIGURE 4
FIGURE 4
The potential therapeutic effect of NPs on the inflammatory response, neuronal death, depolarization of the nerve, and BBB disruption in CNS-diseases including AD, PD, HD, ALS, and MS.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Agostinho P., A. Cunha R., Oliveira C. (2010). Neuroinflammation, Oxidative Stress and the Pathogenesis of Alzheimers Disease. Cpd 16 (25), 2766–2778. 10.2174/138161210793176572 - DOI - PubMed
    1. Agrawal M., Saraf S., Saraf S., Antimisiaris S. G., Chougule M. B., Shoyele S. A., et al. (2018). Nose-to-brain Drug Delivery: An Update on Clinical Challenges and Progress towards Approval of Anti-alzheimer Drugs. J. Control. Release 281, 139–177. 10.1016/j.jconrel.2018.05.011 - DOI - PubMed
    1. Agrawal M., Tripathi D. K., Mourtas S., Saraf S., Antimisiaris S. G., Hammarlund-Udenaes M., et al. (2017). Recent Advancements in Liposomes Targeting Strategies to Cross Blood-Brain Barrier (BBB) for the Treatment of Alzheimer's Disease. J. Control. Release 260, 61–77. 10.1016/j.jconrel.2017.05.019 - DOI - PubMed
    1. Alawieyah Syed Mortadza S., Sim J. A., Neubrand V. E., Jiang L. H. (2018). A Critical Role of TRPM2 Channel in Abeta42 -induced Microglial Activation and Generation of Tumor Necrosis Factor-Alpha. Glia 66 (3), 562–575. 10.1002/glia.23265 - DOI - PubMed
    1. Alcendor D. J., Charest A. M., Zhu W. Q., Vigil H. E., Knobel S. M. (2012). Infection and Upregulation of Proinflammatory Cytokines in Human Brain Vascular Pericytes by Human Cytomegalovirus. J. Neuroinflammation 9, 95. 10.1186/1742-2094-9-95 - DOI - PMC - PubMed