Neuronanomedicine: An Up-to-Date Overview
Abstract
:1. Introduction
2. Nanocarriers for Brain Targeting
2.1. Organic Nanocarriers
2.1.1. Polymeric Nanoparticles
2.1.2. Solid-Lipid Nanoparticles
2.1.3. Liposomes
2.1.4. Dendrimers
2.1.5. Micelles
2.2. Inorganic Nanocarriers
2.2.1. Inorganic Nanoparticles
2.2.2. Carbon Nanotubes
2.2.3. Quantum Dots
2.3. Biological Vectors
2.3.1. Viral Vectors
2.3.2. Extracellular Vesicles
3. Nanomedicine in Central Nervous System Disorders
3.1. Brain Cancer
3.2. Neurodegenerative Diseases
3.3. Stroke
3.4. Clinical Applications
4. Challenges and Limitations
5. Conclusions and Perspectives
Author Contributions
Conflicts of Interest
References
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Nanocarrier Type | Advantages | Disadvantages | Surface Functionalization Strategies |
---|---|---|---|
Polymeric nanoparticles | biocompatibility, biodegradability, drug protection, ease of preparation, good tolerance controlled pharmacokinetics tunable physicochemical properties | neurotoxicity | polysorbate 80 RVG29 peptide anti-Aβ1-42 antibody monoclonal antibody (OX26) anti-Aβ (DE2B4) g7 ligand TGN peptides QSH peptides l-valine chlorotoxin |
Solid-lipid nanoparticles | biocompatibility, high physical stability, bioavailability, drug protection, strict control of release, ease of preparation, good tolerance, and biodegradability without generating toxic by-products no neurotoxic effects reported hydrophobic drug entrapment efficiency lipophilicity possibility of passively cross the BBB | reduced hydrophilic drug entrapment efficiency sterilization difficulties | apolipoprotein E |
Liposomes | possibility of entrapping both hydrophilic and hydrophobic compounds improved drug protection and targeting efficiency lipophilicity possibility of passively cross the BBB | neurotoxicity physicochemical instability tendency of fusion rapid clearance sterilization difficulties | phosphatidylserine-targeting antibody polyethylene glycol transferrin PFVYLI peptide penetratin peptide glucose-vitamin C complex phosphatidic acid apolipoprotein E |
Dendrimers | possibility of entrapping both hydrophilic and hydrophobic compounds biodegradability stimuli-responsiveness enhanced targeting efficiency | neurotoxicity synthesis variability rapid clearance organ accumulation | polyethylene glycol glioma homing peptides sialic acid glucosamine concanavalin A |
Micelles | no neurotoxic effects reported improved drug bioavailability physicochemical stability sustained and controlled release | use only for lipophilic drugs low drug loading capacity | Tween 80 |
Inorganic nanoparticles | unique optical, electrical, and magnetic properties tunable size, shape, composition, structure, and porosity prolonged enhanced permeability and retention effect enhanced on-demand drug release by applying external stimuli (near-infrared radiation and magnetic field) | neurotoxicity high tendency of aggregation non-degradableorgan accumulation need further functionalization for BBB crossing | cyclo RGD peptides phosphonate polyethylene glycol bovine serum albumin folic acid CBP4 peptide KLVFF and LPFFD peptides CLPFFD peptides l-DOPA hif-prolyl hydroxylase 2 silencing |
Carbon nanotubes | unique structure, exceptional electrical, mechanical, optical, and thermal properties, and high surface area | neurotoxicity need further functionalization for BBB crossing | Pittsburgh Compound B polysorbate and phospholipid coating |
Quantum dots | exceptional optical and electrical properties | neurotoxicity need further functionalization for BBB crossing | polyethylene glycol asparagine-glycine-arginine peptides |
Central Nervous System Disorder | Nanocarrier Type | Functionalization | Imaging Agent | Neuroimaging Technique | Study Model | Reference |
---|---|---|---|---|---|---|
Brain cancer | silica shells double coated with semiconducting polymer layers | cyclo RGD peptides | - | fluorescence and photoacoustic brightness imaging | in vitro—4T1 human breast cancer epithelial cells in vivo—tumor-bearing female mice | [79] |
iron oxide nanoparticles | phosphonate polyethylene glycol and cyclo RGD peptides | - | magnetic resonance imaging | in vitro—U87-MG cells in vivo—tumor-bearing nude mice | [80] | |
bovine serum albumin and tumor-specific folic acid | fluorescein isothiocyanate | magnetic resonance imaging | in vitro—U251 cells | [81] | ||
gold nanoparticles | CBP4 peptide | fluorescein isothiocyanate | confocal microscopy | in vitro—U373 human glioma cells | [82] | |
liposomes | - | heptamethine cyanine dye IR780 | near-infrared fluorescence imaging | in vitro—U87MG human glioma cells and T98G human glioblastoma cells in vivo—glioblastoma mouse models | [46] | |
phosphatidylserine-targeting antibody | iron oxide nanoparticles and a near-infrared fluorescence dye | near-infrared fluorescence imaging and magnetic resonance imaging | in vitro—U87MG human glioma cells in vivo—tumor-bearing nude mice | [83] | ||
micelles | - | gadolinium | magnetic resonance imaging | in vivo—Wistar male rats | [84] | |
quantum dots | polyethylene glycol and asparagine–glycine–arginine peptides | - | IVIS imaging | in vitro—primary rat BCECs, astrocytes and C6 glioma cells in vivo—Sprague–Dawley male rats | [85] | |
Neurodegenerative diseases | gadolinium-based nanoparticles | KLVFF and LPFFD peptides | - | fluorescence microscopy | in vivo—APPswe/PS1A246E/TTR mouse model | [103] |
carbon nanotubes | Pittsburgh Compound B | gadolinium complexes | single photon emission computed tomography/computed tomography and γ-scintigraphy | in vivo—female C57BL/6 mice | [104] | |
Stroke | Iron-oxide nanoparticles | - | - | microwave imaging | in vitro—gel brain phantom in vivo—New Zealand rabbits and a middle-aged human male | [124] |
Central Nervous System Disorder | Nanocarrier Type | Functionalization | Active Compound | Study Model | Reference |
---|---|---|---|---|---|
Brain cancer | poly(lactide-co-glycolic) nanoparticles | poloxamer 188 | doxorubicin | in vitro—U-87 MG, ATCC cell line | [86] |
- | cisplatin and boldine | in vivo – tumor-bearing swiss albino mice | [87] | ||
polyethylene glycol and poly(ω-pentadecalactone-co-p-dioxanone) nanoparticles | - | VE822 | in vitro—RG2 cells in vivo —Tumor-bearing male Fischer 344 rats | [88] | |
polyethylene glycol and poly(lactic-co-glycolic) acid nanoparticles | RVG29 peptide | docetaxel | in vitro—C6 cells in vivo—tumor-bearing adult Sprague–Dawley male rats | [89] | |
amphiphilic polymer-lipid nanoparticles | polysorbate 80 | docetaxel | in vitro—MDA-MB-231 cells in vivo—tumor-bearing severe combined immune deficiency mice | [90] | |
liposomes | polyethylene glycol | methotrexate | in vivo – male Sprague–Dawley rats | [91] | |
transferrin and PFVYLI peptide | doxorubicin and erlotinib | in vitro—U87 tumor cells, brain endothelial cells, and glial cells | [92] | ||
transferrin and penetratin peptide | 5-fluorouracil | in vitro—U87 tumor cells and brain endothelial cells | [93] | ||
glucose-vitamin C complex | paclitaxel | in vitro—C6 cells in vivo—C6 glioma-bearing Kunming mice | [94] | ||
dendrimers | polyethylene glycol and glioma homing peptides | - | in vitro—U87MG cells in vivo—U87MG tumor-bearing BALB/c nude mice | [95] | |
sialic acid, glucosamine, and concanavalin A | paclitaxel | in vitro—U373MG human astrocytoma cell line in vivo—Sprague–Dawley rats | [96] | ||
micelles | Tween 80 | curcumin | in vitro—G422 cells | [97] | |
multi-walled carbon nanotubes | Angiopep-2 | - | in vitro—primary porcine brain endothelial cells and primary rat astrocytes in vivo—GL261 glioma-bearing female C57/Bl6 mice | [98] | |
USPIONS | - | - | in vitro—rat CNS-1 cells | [99] | |
Neurodegenerative diseases | polyethylene glycol nanoparticles | anti-Aβ1-42 antibody | - | in vivo—NIHS adult male mice | [105] |
poly(lactic-co-glycolic) acid nanoparticles | monoclonal antibody (OX26) and anti-Aβ (DE2B4) | - | in vitro—porcine brain capillary endothelial cells | [106] | |
poly(lactic-co-glycolic) acid nanoparticles | g7 ligand | curcumin | in vitro—primary hippocampal cultures from rat brains | [108] | |
polyethylene glycol-polylactic acid nanoparticles | TGN peptides and QSH peptides | coumarin-6 and H102 | in vitro—brain endothelial cells in vivo—5XFAD transgenic mice | [107] | |
chitosan nanoparticles | L-valine | saxagliptin | in vivo—female Wistar rats | [109] | |
- | selegiline | ex vivo—male Sprague–Dawley rats | [110] | ||
- | pramipexole dihydrochloride | ex vivo—goat nasal mucosa in vivo—male Sprague–Dawley rats | [111] | ||
liposomes | phosphatidic acid and apolipoprotein E | quercetin and rosmarinic acid | in vitro—brain microvascular endothelial cells and Aβ1-42-insulted SK-N-MC cells | [112] | |
transferrin | α-mangostin | in vitro—brain endothelial cells in vivo—Sprague–Dawley rats | [113] | ||
polyamidoamine dendrimers | - | carbamazepine | ex vivo—human red blood cells in vitro—N2a cell linein vivo—zebrafish | [114] | |
micelles | - | curcumin | in vitro—U87MG cell line in vivo—female Sprague–Dawley rats | [115] | |
gold nanoparticles | CLPFFD peptides, neutral methoxy terminated polyethylene glycol ligands, and negatively-charged monosulfonated triphenylphosphine ligands | - | in vitro—porcine brain capillary endothelial | [116] | |
L-DOPA | - | in vitro—human brain endothelial cell line hCMEC/D3, brain microvascular endothelial cells, and mouse microglia N9 cell line | [118] | ||
multi-walled carbon nanotubes | polysorbate and phospholipid coating | berberine | in vitro—human red blood cells and SH-SY5Y cells in vivo—male Wistar rats | [117] | |
cerium oxide nanoparticles | - | - | in vivo—adult male Wistar rats | [119] | |
Stroke | poly(lactic-co-glycolic) acid nanoparticles | chlorotoxin | Lexiscan and Nogo-66 | in vivo—male C57BL/6 mice | [125] |
polyamidoamine dendrimers | polyethylene glycol | - | in vitro—rat primary astrocytes and mouse brain endothelial cells in vivo—male C57BL/6 mice | [126] | |
iron oxide nanoparticles | hif-prolyl hydroxylase 2 silencing | siRNA | in vivo—female BALB/c nude mice | [127] |
Nanocarrier Type | Neurotoxic Effect |
---|---|
Polymeric nanoparticles | neuronal apoptosis; neuroinflammation; increased oxidative stress |
Liposomes | necrosis; neuroinflammation; hemorrhage; macrophage infiltration |
Dendrimers | cell proliferation and migration inhibition; abnormal mitochondrial activity; apoptosis; affected neuronal differentiation; increased oxidative stress; DNA damage; decreased locomotor function |
Gold nanoparticles | increased oxidative stress; cognition defects; astrogliosis |
Silver nanoparticles | increased oxidative stress; apoptosis; necrosis; neuroinflammation |
Iron oxide nanoparticles | synaptic transmission and nerve conduction alterations; neuroinflammation; apoptosis; macrophage infiltration |
Titanium oxide nanoparticles | increased oxidative stress; neuroinflammation; apoptosis; synaptic transmission alterations and plasticity; genotoxicity |
Silica nanoparticles | cognitive dysfunctions and impairment; neurodegeneration; synaptic transmission alterations |
Carbon nanotubes | neuroinflammation; cell proliferation inhibition; apoptosis; increased oxidative stress; mitochondrial membrane potential reduction; lipid peroxidization; astrocyte function reduction; neurobehavioral toxicity |
Quantum dots | increased oxidative stress; cell function damage; neurobehavioral toxicity; cognitive impairment |
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Teleanu, D.M.; Chircov, C.; Grumezescu, A.M.; Teleanu, R.I. Neuronanomedicine: An Up-to-Date Overview. Pharmaceutics 2019, 11, 101. https://doi.org/10.3390/pharmaceutics11030101
Teleanu DM, Chircov C, Grumezescu AM, Teleanu RI. Neuronanomedicine: An Up-to-Date Overview. Pharmaceutics. 2019; 11(3):101. https://doi.org/10.3390/pharmaceutics11030101
Chicago/Turabian StyleTeleanu, Daniel Mihai, Cristina Chircov, Alexandru Mihai Grumezescu, and Raluca Ioana Teleanu. 2019. "Neuronanomedicine: An Up-to-Date Overview" Pharmaceutics 11, no. 3: 101. https://doi.org/10.3390/pharmaceutics11030101
APA StyleTeleanu, D. M., Chircov, C., Grumezescu, A. M., & Teleanu, R. I. (2019). Neuronanomedicine: An Up-to-Date Overview. Pharmaceutics, 11(3), 101. https://doi.org/10.3390/pharmaceutics11030101