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Microglia nanoparticles

Neal K Bennett, Rebecca Chmielowski, Dalia S Abdelhamid, Jonathan J Faig, Nicola Francis, Jean Baum, Zhiping P Pang, Kathryn E Uhrich, Prabhas V Moghe
Neuroinflammation, a common neuropathologic feature of neurodegenerative disorders including Parkinson disease (PD), is frequently exacerbated by microglial activation. The extracellular protein α-synuclein (ASYN), whose aggregation is characteristic of PD, remains a key therapeutic target, but the control of synuclein trafficking and aggregation within microglia has been challenging. First, we established that microglial internalization of monomeric ASYN was mediated by scavenger receptors (SR), CD36 and SRA1, and was rapidly accompanied by the formation of ASYN oligomers...
December 2016: Biomaterials
Anuj Kumar Sharma, Vikas Singh, Ruchi Gera, Mahaveer Prasad Purohit, Debabrata Ghosh
Zinc oxide nanoparticle (ZnO-NP) is one of the most widely used engineered nanoparticles. Upon exposure, nanoparticle can eventually reach the brain through various routes, interact with different brain cells, and alter their activity. Microglia is the fastest glial cell to respond to any toxic insult. Nanoparticle exposure can activate microglia and induce neuroinflammation. Simultaneous to activation, microglial death can exacerbate the scenario. Therefore, we focused on studying the effect of ZnO-NP on microglia and finding out the pathway involved in the microglial death...
October 6, 2016: Molecular Neurobiology
Runze Yang, Susobhan Sarkar, Daniel J Korchinski, Ying Wu, V Wee Yong, Jeff F Dunn
BACKGROUND: Glioblastoma (GBM) is an aggressive brain cancer with a poor prognosis. The use of immune therapies to treat GBM has become a promising avenue of research. It was shown that amphotericin B (Amp B) can stimulate the innate immune system and suppress the growth of brain tumor initiating cells (BTICs). However, it is not feasible to use histopathology to determine immune activation in patients. We developed an MRI technique that can rapidly detect a therapeutic response in animals treated with drugs that stimulate innate immunity...
August 29, 2016: Neuro-oncology
Tian Xie, Ankit Vora, Patrick J Mulcahey, Sonia E Nanescu, Manpreet Singh, Daniel S Choi, Jeffrey K Huang, Chi-Chun Liu, Daniel P Sanders, Jong-In Hahm
The ability to control the specific adsorption and packing behaviors of biomedically important proteins by effectively guiding their preferred surface adsorption configuration and packing orientation on polymeric surfaces may have utility in many applications such as biomaterials, medical implants, and tissue engineering. Herein, we investigate the distinct adhesion configurations of fibrinogen (Fg) proteins and the different organization behaviors between single Fg molecules that are mediated by the changes in the periodicity and alignment of chemically alternating nanodomains in thin films of polystyrene-block-poly(methyl methacrylate) (PS-b-PMMA) block copolymer (BCP)...
August 23, 2016: ACS Nano
Ghasem Ghalamfarsa, Mohammad Hojjat-Farsangi, Mousa Mohammadnia-Afrouzi, Enayat Anvari, Shohreh Farhadi, Mehdi Yousefi, Farhad Jadidi-Niaragh
Multiple sclerosis (MS) is an autoimmune neurodegenerative disease characterized with immunopathobiological events, including lymphocytic infiltration into the central nervous system (CNS), microglia activation, demyelination and axonal degeneration. Although several neuroprotective drugs have been designed for the treatment of MS, complete remission is yet matter of debate. Therefore, development of novel therapeutic approaches for MS is of a high priority in immunological research. Nanomedicine is a recently developed novel medical field, which is applicable in both diagnosis and treatment of several cancers and autoimmune diseases...
September 2016: Journal of Immunotoxicology
Crystal S Lewis, Luisa Torres, Jeremy T Miyauchi, Cyrus Rastegar, Jonathan M Patete, Jacqueline M Smith, Stanislaus S Wong, Stella E Tsirka
Understanding the nature of interactions between nanomaterials, such as commercially ubiquitous hematite (α-Fe2O3) Nanorhombohedra (N-Rhomb) and biological systems is of critical importance for gaining insight into the practical applicability of nanomaterials. Microglia represent the first line of defense in the central nervous system (CNS) during severe injury or disease such as Parkinson's and Alzheimer's disease as illustrative examples. Hence, to analyze the potential cytotoxic effect of nanorhombohedra exposure in the presence of microglia, we have synthesized Rhodamine B (RhB) labeled-α-Fe2O3 N-Rhomb, with lengths of 47 ± 10 nm and widths of 35 ± 8 nm...
May 1, 2016: Toxicology Research
I-Lun Hsiao, Chia-Cheng Chang, Chung-Yi Wu, Yi-Kong Hsieh, Chun-Yu Chuang, Chu-Fang Wang, Yuh-Jeen Huang
Although, titanium dioxide nanoparticles (TiO2NPs) are nanomaterials commonly used in consumer products, little is known about their hazardous effects, especially on central nervous systems. To examine this issue, ALT astrocyte-like, BV-2 microglia and differentiated N2a neuroblastoma cells were exposed to 6 nm of 100% anatase TiO2NPs. A lipopolysaccharide (LPS) was pre-treated to activate glial cells before NP treatment for mimicking NP exposure under brain injury. We found that ALT and BV-2 cells took up more NPs than N2a cells and caused lower cell viability...
July 25, 2016: Chemico-biological Interactions
Abhishek Umashankar, Mandi J Corenblum, Sneha Ray, Michel Valdez, Eriko S Yoshimaru, Theodore P Trouard, Lalitha Madhavan
An essential component of developing successful neural stem cell (NSC)-based therapies involves the establishment of methodologies to noninvasively monitor grafted NSCs within brain tissues in real time. In this context, ex vivo labeling with ultrasmall superparamagnetic iron oxide (USPIO) particles has been shown to enable efficient tracking of transplanted NSCs via magnetic resonance imaging (MRI). However, whether and how USPIO labeling affects the intrinsic biology of NSCs is not thoroughly understood, and remains an active area of investigation...
2016: International Journal of Nanomedicine
Joshua C Grimm, J Trent Magruder, Mary A Wilson, Mary E Blue, Todd C Crawford, Juan C Troncoso, Fan Zhang, Sujatha Kannan, Christopher M Sciortino, Michael V Johnston, Rangaramanujam M Kannan, William A Baumgartner
BACKGROUND: Neurocognitive dysfunction and injury remain problematic after cardiac procedures requiring hypothermic circulatory arrest (HCA). Due to poor blood-brain barrier penetrance and toxicities associated with systemic drug therapies, clinical success has been elusive. Accordingly, we explored targeted dendrimer (a nanoparticle) drug therapies in our well-established canine model of HCA to characterize the biodistribution and cellular localization of these nanoparticles in areas of known neuronal apoptosis and necrosis...
September 2016: Annals of Thoracic Surgery
Zhizhi Sun, Matthew Worden, James A Thliveris, Sabine Hombach-Klonisch, Thomas Klonisch, Johan van Lierop, Torsten Hegmann, Donald W Miller
Effective treatment of brain disorders requires a focus on improving drug permeability across the blood-brain barrier (BBB). Herein, we examined the pharmacokinetic properties of negatively charged iron oxide nanoparticles (IONPs) and the capability of using lysophosphatidic acid (LPA) to transiently disrupt the tight junctions and allow IONPs to enter the brain. Under normal conditions, IONPs had a plasma half-life of six minutes, with the liver and spleen being the major organs of IONP deposition. Treatment with LPA enhanced accumulation of IONPs in the brain and spleen (approximately 4-fold vs control)...
April 25, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Stephen L Hayward, Christina L Wilson, Srivatsan Kidambi
Glioblastoma Multiforme (GBM) is a highly prevalent and deadly brain malignancy characterized by poor prognosis and restricted disease management potential. Despite the success of nanocarrier systems to improve drug/gene therapy for cancer, active targeting specificity remains a major hurdle for GBM. Additionally, since the brain is a multi-cell type organ, there is a critical need to develop an approach to distinguish between GBM cells and healthy brain cells for safe and successful treatment. In this report, we have incorporated hyaluronic acid (HA) as an active targeting ligand for GBM...
June 7, 2016: Oncotarget
Hsin-I Tong, Wen Kang, Philip M C Davy, Yingli Shi, Si Sun, Richard C Allsopp, Yuanan Lu
The ability of monocytes and monocyte-derived macrophages (MDM) to travel towards chemotactic gradient, traverse tissue barriers, and accumulate precisely at diseased sites makes them attractive candidates as drug carriers and therapeutic gene delivery vehicles targeting the brain, where treatments are often hampered by the blockade of the blood brain barrier (BBB). This study was designed to fully establish an optimized cell-based delivery system using monocytes and MDM, by evaluating their homing efficiency, engraftment potential, as well as carriage and delivery ability to transport nano-scaled particles and exogenous genes into the brain, following the non-invasive intravenous (IV) cell adoptive transfer in an acute neuroinflammation mouse model induced by intracranial injection of Escherichia coli lipopolysaccharides...
2016: PloS One
Junran Xie, Dongju Xiao, Jinning Zhao, Nianqiang Hu, Qi Bao, Li Jiang, Lina Yu
The long-term use of potent analgesics is often needed to treat chronic pain. However, it has been greatly hindered by their side effects such as addiction and withdrawal reactions. The study seeks to circumvent these drawbacks by taking advantage of a multifunctional delivery system based on nanoparticles to target on pathological neuroinflammation. A drug delivery system is designed and generated using mesoporous silica nanoparticles (MSNs) that are loaded with Δ9-THC (Δ9-tetrahydrocannabinol, a cannabinoid) and ARA290 (an erythropoietin-derived polypeptide), both of which possess analgesic and anti-inflammatory functions...
May 2016: Advanced Healthcare Materials
Fan Zhang, Elizabeth Nance, Yossef Alnasser, Rangaramanujam Kannan, Sujatha Kannan
BACKGROUND: Microglial cells have been implicated in neuroinflammation-mediated injury in the brain, including neurodevelopmental disorders such as cerebral palsy (CP) and autism. Pro-inflammatory activation of microglial cells results in the impairment of their neuroprotective functions, leading to an exaggerated, ongoing immune dysregulation that can persist long after the initial insult. We have previously shown that dendrimer-mediated delivery of an anti-inflammatory agent can attenuate inflammation in a rabbit model of maternal inflammation-induced CP and significantly improve the motor phenotype, due to the ability of the dendrimer to selectively localize in activated microglia...
2016: Journal of Neuroinflammation
Jana Zielinski, Anja-Maria Möller, Martin Frenz, Meike Mevissen
Silica nanoparticles embedded in a biodegradable scaffold have been proposed to offer several advantages when used in laser-tissue-soldering of blood vessels in the brain. During degradation, these nanoparticles are likely to be released into the surrounding brain tissue. The aim of this study was to investigate possible cellular uptake mechanism(s) of the two silica nanoparticle types in microglial cells as well as their effect on autophagy and inflammatory cytokines. The nanoparticle uptake was analysed quantitatively using high-content analysis...
August 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Milagros Ramos-Gómez, Alberto Martínez-Serrano
Human neural stem cells (hNSCs) derived from the ventral mesencephalon are powerful research tools and candidates for cell therapies in Parkinson's disease. However, their clinical translation has not been fully realized due, in part, to the limited ability to track stem cell regional localization and survival over long periods of time after in vivo transplantation. Magnetic resonance imaging provides an excellent non-invasive method to study the fate of transplanted cells in vivo. For magnetic resonance imaging cell tracking, cells need to be labeled with a contrast agent, such as magnetic nanoparticles, at a concentration high enough to be easily detected by magnetic resonance imaging...
January 2016: Neural Regeneration Research
Emma Portnoy, Boris Polyak, Dorrit Inbar, Gilad Kenan, Ahmad Rai, Suzanne L Wehrli, Timothy P L Roberts, Ameer Bishara, Aniv Mann, Miriam Shmuel, Katya Rozovsky, Gal Itzhak, Tamir Ben-Hur, Shlomo Magdassi, Dana Ekstein, Sara Eyal
Correct localization of epileptic foci can improve surgical outcome in patients with drug-resistant seizures. Our aim was to demonstrate that systemically injected nanoparticles identify activated immune cells, which have been reported to accumulate in epileptogenic brain tissue. Fluorescent and magnetite-labeled nanoparticles were injected intravenously to rats with lithium-pilocarpine-induced chronic epilepsy. Cerebral uptake was studied ex vivo by confocal microscopy and MRI. Cellular uptake and biological effects were characterized in vitro in murine monocytes and microglia cell lines...
July 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Susana R Cerqueira, Joaquim M Oliveira, Nuno A Silva, Hugo Leite-Almeida, Silvina Ribeiro-Samy, Armando Almeida, João F Mano, Nuno Sousa, António J Salgado, Rui L Reis
No abstract text is available yet for this article.
February 24, 2016: Small
Lei Yao, Xiao Gu, Qingxiang Song, Xiaolin Wang, Meng Huang, Meng Hu, Lina Hou, Ting Kang, Jun Chen, Hongzhuan Chen, Xiaoling Gao
Alzheimer's disease (AD), the most common form of dementia, is now representing one of the largest global healthcare challenges. However, an effective therapy is still lacking. Accumulation of amyloid-beta (Aβ) in the brain is supposed to trigger pathogenic cascades that eventually lead to AD. Therefore, Aβ clearance strategy is being actively pursued as a promising disease modifying therapy. Here, we found that α-mangostin (α-M), a polyphenolic xanthone derivative from mangosteen, up-regulated low density lipoprotein receptor (LDLR) expression in microglia and liver cells, and efficiently facilitated Aβ clearance...
March 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Stuart I Jenkins, Daniel Weinberg, Arwa F Al-Shakli, Alinda R Fernandes, Humphrey H P Yiu, Neil D Telling, Paul Roach, Divya M Chari
Surface engineering to control cell behavior is of high interest across the chemical engineering, drug delivery and biomaterial communities. Defined chemical strategies are necessary to tailor nanoscale protein interactions/adsorption, enabling control of cell behaviors for development of novel therapeutic strategies. Nanoparticle-based therapies benefit from such strategies but particle targeting to sites of neurological injury remains challenging due to circulatory immune clearance. As a strategy to overcome this barrier, the use of stealth coatings can reduce immune clearance and prolong circulatory times, thereby enhancing therapeutic capacity...
February 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
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