Targeting with nanoparticles for the therapeutic treatment of brain diseases

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Brain diseases including neurodegenerative disorders and tumours are among the most serious health problems, degrading the quality of life and causing massive economic cost. Nanoparticles that load and deliver drugs and genes have been intensively studied for the treatment of brain diseases, and have demonstrated some biological effects in various animal models. Among other efforts taken in the nanoparticle development, targeting of blood brain barrier, specific cell type or local intra-/extra-cellular space is an important strategy to enhance the therapeutic efficacy of the nanoparticle delivery systems. This review underlies the targeting issue in the nanoparticle development for the treatment of brain diseases, taking key exemplar studies carried out in various in vivo models.

Related collections

Most cited references 45

Record: found
Abstract: found
Article: not found

Mitochondria-Targeting Ceria Nanoparticles as Antioxidants for Alzheimer's Disease.

Hyek Kwon, Moon-Yong Cha, Dokyoon Kim … (2016)

Mitochondrial oxidative stress is a key pathologic factor in neurodegenerative diseases, including Alzheimer's disease. Abnormal generation of reactive oxygen species (ROS), resulting from mitochondrial dysfunction, can lead to neuronal cell death. Ceria (CeO2) nanoparticles are known to function as strong and recyclable ROS scavengers by shuttling between Ce(3+) and Ce(4+) oxidation states. Consequently, targeting ceria nanoparticles selectively to mitochondria might be a promising therapeutic approach for neurodegenerative diseases. Here, we report the design and synthesis of triphenylphosphonium-conjugated ceria nanoparticles that localize to mitochondria and suppress neuronal death in a 5XFAD transgenic Alzheimer's disease mouse model. The triphenylphosphonium-conjugated ceria nanoparticles mitigate reactive gliosis and morphological mitochondria damage observed in these mice. Altogether, our data indicate that the triphenylphosphonium-conjugated ceria nanoparticles are a potential therapeutic candidate for mitochondrial oxidative stress in Alzheimer's disease.

0 comments Cited 192 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Transport of drugs across the blood-brain barrier by nanoparticles.

Jörg Kreuter, S Wohlfart, Svetlana Gelperina (2012)

The central nervous system is well protected by the blood-brain barrier (BBB) which maintains its homeostasis. Due to this barrier many potential drugs for the treatment of diseases of the central nervous system (CNS) cannot reach the brain in sufficient concentrations. One possibility to deliver drugs to the CNS is the employment of polymeric nanoparticles. The ability of these carriers to overcome the BBB and to produce biologic effects on the CNS was shown in a number of studies. Over the past few years, progress in understanding of the mechanism of the nanoparticle uptake into the brain was made. This mechanism appears to be receptor-mediated endocytosis in brain capillary endothelial cells. Modification of the nanoparticle surface with covalently attached targeting ligands or by coating with certain surfactants enabling the adsorption of specific plasma proteins are necessary for this receptor-mediated uptake. The delivery of drugs, which usually are not able to cross the BBB, into the brain was confirmed by the biodistribution studies and pharmacological assays in rodents. Furthermore, the presence of nanoparticles in the brain parenchyma was visualized by electron microscopy. The intravenously administered biodegradable polymeric nanoparticles loaded with doxorubicin were successfully used for the treatment of experimental glioblastoma. These data, together with the possibility to employ nanoparticles for delivery of proteins and other macromolecules across the BBB, suggest that this technology holds great promise for non-invasive therapy of the CNS diseases. Copyright © 2011 Elsevier B.V. All rights reserved.

0 comments Cited 173 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Microglial Activation in Traumatic Brain Injury

Cornelius K Donat, Gregory Scott, Steve Gentleman … (2017)

Microglia have a variety of functions in the brain, including synaptic pruning, CNS repair and mediating the immune response against peripheral infection. Microglia rapidly become activated in response to CNS damage. Depending on the nature of the stimulus, microglia can take a number of activation states, which correspond to altered microglia morphology, gene expression and function. It has been reported that early microglia activation following traumatic brain injury (TBI) may contribute to the restoration of homeostasis in the brain. On the other hand, if they remain chronically activated, such cells display a classically activated phenotype, releasing pro-inflammatory molecules, resulting in further tissue damage and contributing potentially to neurodegeneration. However, new evidence suggests that this classification is over-simplistic and the balance of activation states can vary at different points. In this article, we review the role of microglia in TBI, analyzing their distribution, morphology and functional phenotype over time in animal models and in humans. Animal studies have allowed genetic and pharmacological manipulations of microglia activation, in order to define their role. In addition, we describe investigations on the in vivo imaging of microglia using translocator protein (TSPO) PET and autoradiography, showing that microglial activation can occur in regions far remote from sites of focal injuries, in humans and animal models of TBI. Finally, we outline some novel potential therapeutic approaches that prime microglia/macrophages toward the beneficial restorative microglial phenotype after TBI.

0 comments Cited 167 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): J Tissue Eng

Journal ID (iso-abbrev): J Tissue Eng

Journal ID (publisher-id): TEJ

Journal ID (hwp): sptej

Title: Journal of Tissue Engineering

Publisher: SAGE Publications (Sage UK: London, England )

ISSN (Electronic): 2041-7314

Publication date (Electronic): 4 March 2020

Publication date Collection: Jan-Dec 2020

Volume: 11

Electronic Location Identifier: 2041731419897460

Affiliations

[1 ]Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea

[2 ]Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, Republic of Korea

[3 ]Department of Nanobiomedical Science and BK21 PLUS Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Republic of Korea

[4 ]UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, Republic of Korea

[5 ]Division of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute, London, UK

Author notes

[*]Hae-Won Kim, Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Republic of Korea. Email: kimhw@ 123456dku.edu

[*]

Authors equally contributed to this work

Author information

Hae-Won Kim https://orcid.org/0000-0001-6400-6100

Article

Publisher ID: 10.1177_2041731419897460

DOI: 10.1177/2041731419897460

PMC ID: 7057401

PubMed ID: 32180936

SO-VID: 31897dd4-413d-45ba-8aa4-c28c56a35a32

License:

This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

History

Date received : 26 August 2019

Date accepted : 5 December 2019

Funding

Funded by: National Research Foundation of Korea, FundRef https://doi.org/10.13039/501100003725;

Award ID: 2018K1A4A3A01064257

Funded by: National Research Foundation of Korea, FundRef https://doi.org/10.13039/501100003725;

Award ID: 2018R1A2B3003446

Funded by: National Research Foundation of Korea, FundRef https://doi.org/10.13039/501100003725;

Award ID: 2018R1D1A1B07048459

Custom metadata

cover-date January-December 2020

typesetter ts1

ScienceOpen disciplines: Biomedical engineering

Keywords: brain diseases,nanoparticles,targeting,blood brain barrier,in vivo models

Data availability:

ScienceOpen disciplines: Biomedical engineering

Keywords: brain diseases, nanoparticles, targeting, blood brain barrier, in vivo models

Targeting with nanoparticles for the therapeutic treatment of brain diseases

Read this article at

Abstract

Related collections

Nanoparticles to cross the blood-brain barrier (BBB)

Most cited references 45

Mitochondria-Targeting Ceria Nanoparticles as Antioxidants for Alzheimer's Disease.

Transport of drugs across the blood-brain barrier by nanoparticles.

Microglial Activation in Traumatic Brain Injury

Author and article information

Journal

Affiliations

Author notes

Author information

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 609

Cited by 18

Most referenced authors 669