Nanoparticle-Based Strategies to Treat Neuro-Inflammation
Abstract
:1. Introduction
1.1. “Nanotechnology”: An Historical Perspective
1.2. “Nanotechnology” Today: A Buzzword
1.3. About Neuro-Inflammation
- (i)
- The first step is initiated upon recognition of the danger signals by microglia, its purpose is to eliminate the triggering element. It is characterized by the expression of class II antigen presenting molecules (MHC II) and costimulatory molecules (CD80, CD86), and by the secretion of pro-inflammatory cytokines (TNFα, IL-1β, IL-12…), chemokines (CCL2, CCL5…), nitric oxide (NO), and reactive oxygen species (ROS, such as superoxide anions). All are necessary to eradicate the aggressive agent;
- (ii)
- Then comes a phase of resolution of the inflammation characterized by the secretion of anti-inflammatory molecules (among others, the anti-inflammatory cytokines IL-10 and TGFβ), and tissue repair factors. This phase allows the arrest of the acute step, the healing of the injured tissue, and the return to homeostasis. A major difference with the systemic inflammatory response is that this resolution phase mediated by microglia also promotes neuroprotection and neuroreparation. On the one hand, neuroprotection is mediated through the synthesis of neurotrophic factors such as Insulin-like Growth Factor 1 (IGF1), Brain-Derived Neurotrophic Factor (BDNF), and Glial cell-Derived Neurotrophic Factor (GDNF). On the other hand, neuroreparation is mediated through the stimulation of neurogenesis by microglia, and through the plasticity of neural circuits.
1.4. About Blood-Brain Barrier
2. Engineered Nanoparticles: Promising Candidates to Tackle Neuro-Inflammation
2.1. Different Ways for Engineered Nanoparticles to Access the Central Nervous System
- (i)
- The Carrier-Mediated Transport (CMT) which is used to carry nutrients or endogenous substances into the brain. To name a few: glucose transporter-1 (GLUT-1/Slc2a1) for the uptake of glucose, and L1 and y+ for the uptake of large neutral and cationic essential amino-acids, respectively;
- (ii)
- The Adsorptive-Mediated Transcytosis (AMT) that involves electrostatic interactions between cationic compounds and negative charges of the membrane of endothelial cells prompting the formation of vesicles of endocytosis;
- (iii)
- The Receptor-Mediated Transcytosis (RMT) that relies on the expression of receptors at the luminal plasma membrane of endothelial cells (i.e., directed towards the bloodstream): transferrin receptor (TfR), LDL (Low Density Lipoprotein) Receptor-related Protein 1 and 2 (LRP-1 and -2), insulin receptor and folate receptor. This pathway warrants the entrance of endogenous macromolecules into the CNS.
2.2. Engineered Nanoparticles in Action
- (i)
- To increase blood circulating time thanks to PEG;
- (ii)
- To favor adsorptive-mediated transcytosis due to electrostatic interactions between polycationic CS and negatives charges of the membrane of the endothelial cells;
- (iii)
- To allow receptor-mediated transcytosis because of the high selectivity of OX-26 mAb for the highly expressed TfR. Two hours after intraperitoneal (IP) administration, semi-quantitative analysis revealed that ENPs were mostly located in the hippocampus and that the mean of CS-PEG-OX26 ENPs per optical field was two to three times greater than the one of CS-PEG ENPs. The authors made the proof of principle that these ENPs are able to cross the BBB and reach the brain, making them promising drug delivery systems to the CNS.
3. Discussion
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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ENP Type | Customization (Targeting Ligand) | Therapeutics | Route of Administration and Animal Model | Reference |
---|---|---|---|---|
polyethylene gycol–polylactide–polyglycolide (PEG-PLGA) | Lactoferrin (Lf) targeting the Transferrin Receptor (TfR) on endothelial cells | Urocortin (URO) | Intravenous (IV) Rat model of Parkinson’s disease (PD) | [40] |
PEG-PLGA | Lactoferrin (Lf) targeting the TfR on endothelial cells | Shikonin (SHK) | IV Healthy rats only | [41] |
PLGA | Non applicable (NA) | Curcumin (Cur) | Intraperitoneal (IP) Rat model of Alzheimer’s disease (AD) | [42] |
Tripolyphosphate cross-linked cationic chitosan (CS) | NA | Piperine (PIP) | Intranasal (IN) Rat model of sporadic dementia of AD type | [43] |
Nanostructured Lipid Carrier (NLC) coated with cationic CS | TransActivator of Transcription (TAT) | Glial cell-Derived Neurotrophic Factor (GDNF) | IN Mouse model of PD | [44] |
cationic nanoliposomes (scL) | Single-chain fragment from the variable region of anti-TfR monoclonal antibody (TfRscFv) | siRNA against TNFα | IV Lipopolysaccharide (LPS)-induced neuro-inflammation in mice | [45] |
PEG polymeric poly lactic acid (PLA) | Cationic bovine serum albumin (CBSA) | Tanshinone IIA (TIIA) | Rat model of cerebral ischemic stroke | [46] |
PEG-PLGA | Odorranalectin (OL), targeting l-fucose expressed on the olfactory epithelium | URO | IN Rat model of PD | [47] |
Cationic lipids nanoemulsions (SNE) | NA | siRNA against TNFα | IN LPS-induced neuro-inflammation in rats | [48] |
Poly-Butyl-CyanoAcrylate (PBCA) | Non-ionic surfactants (in particular Tween 80) with or without cationic resin DEAE (both interacting with circulating apoliproprotein E) | NA | IV Healthy rats only | [49] |
Gold nanoparticles (GNP) | Insulin (INS) | NA | IV Healthy mice only | [53] |
CS-PEG | Anti-TfR monoclonal antibody OX26 | NA | IP Healthy mice only | [54] |
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Poupot, R.; Bergozza, D.; Fruchon, S. Nanoparticle-Based Strategies to Treat Neuro-Inflammation. Materials 2018, 11, 270. https://doi.org/10.3390/ma11020270
Poupot R, Bergozza D, Fruchon S. Nanoparticle-Based Strategies to Treat Neuro-Inflammation. Materials. 2018; 11(2):270. https://doi.org/10.3390/ma11020270
Chicago/Turabian StylePoupot, Rémy, Dylan Bergozza, and Séverine Fruchon. 2018. "Nanoparticle-Based Strategies to Treat Neuro-Inflammation" Materials 11, no. 2: 270. https://doi.org/10.3390/ma11020270
APA StylePoupot, R., Bergozza, D., & Fruchon, S. (2018). Nanoparticle-Based Strategies to Treat Neuro-Inflammation. Materials, 11(2), 270. https://doi.org/10.3390/ma11020270