Exosomes as CNS Drug Delivery Tools and Their Applications
Abstract
1. Introduction
2. The Roles of Exosomes in the CNS
2.1. The Blood-Brain Barrier and Its Challenges in the Treatment
2.2. Multiple Functions of CNS Cell-Derived Exosomes
3. Strategies for Drug Loading into Exosomes
3.1. Pre-Secretory Loading
3.2. Post-Secretory Loading
4. Drug Administration Affects the Efficiency of Exosomes into the CNS
5. Engineering Exosomes Enhance the CNS Targeting and Therapeutic Efficacy
6. Research and Applications of Exosomal Drug Delivery Systems in CNS Diseases
6.1. Alzheimer’s Disease
6.2. Parkinson’s Disease
6.3. Huntington’s Disease
6.4. Stroke
6.5. Brain or Spinal Cord Injury and Neuroinflammation
6.6. Brain Tumor
6.7. Other Brain Diseases: Viral Infection; Drug Addiction
7. Conclusions and Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
CNS | central nervous system |
RVG | rabies virus glycoprotein |
DDS | drug delivery system |
BBB | blood-brain barrier |
AAV | adeno-associated virus |
EVs | extracellular vesicles |
MPS | mononuclear phagocytic system |
PEG | polyethylene glycol |
ABC | acceleration of blood clearance |
CSF | cerebrospinal fluid |
MSC | mesenchymal stem cell |
SCI | spinal cord injury |
TBI | traumatic brain injury |
MS | multiple sclerosis |
EAE | experimental allergic encephalomyelitis |
RES | reticuloendothelial system |
PD | Parkinson’s disease |
AD | Alzheimer’s disease |
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---|---|---|---|---|---|---|---|---|
Alzheimer’s disease | self-derived dendritic cells | BACE1 siRNA | electroporation | Lamp2b-RVG | Mice | intravenous | neurons, microglia, and oligodendrocytes | [118] |
Parkinson’s disease | HEK-293T cells | catalase mRNA | transfection | Lamp2b-RVG | Mice | subcutaneous | unknown | [129] |
primary dendritic cells | a-Syn siRNA | electroporation | Lamp2b-RVG | Mice | intravenous | unknown | [142] | |
primary dendritic cells | shRNA-MCs | electroporation | Lamp2b-RVG | Mice | intravenous | unknown | [143] | |
HEK-293T cells | aptamer F5R1 | co-incubation | Lamp2b-RVG | Mice | intraperitoneal | microglia, neurons, and astrocytes | [79] | |
mice blood | dopamine | co-incubation | None | Mice | intravenous | unknown | [80] | |
RAW264.7 | catalase | co-incubation, freeze-thaw, sonication, or extrusion | None | Mice | intranasal | neurons and microglia | [86] | |
Huntington’s disease | glioblastoma U87 cells | hsiRNAHTT | co-incubation | None | Mice | unilateral brain infusion | neurons | [148] |
Stroke | mesenchymal stromal cells (MSC) | curcumin | co-incubation | c(RGDyK) peptide | Mice | intravenous | microglia, neurons, and astrocytes | [123] |
bone marrow mesenchymal stem cells (BMSC) | miR-193b-3p | electroporation | Lamp2b-RVG | Mice | intravenous | unknown | [154] | |
HEK-293T cells | circ SCMH1 | transfection | Lamp2b-RVG | Mice and rhesus monkeys | intravenous | microglia, neurons, and astrocytes | [74] | |
mesenchymal stem cells (MSCs) | miR-223-3p | transfection | None | Rats | intravenous | unknown | [164] | |
RAW264.7 | curcumin | co-incubation | None | Rats | intravenous | neurons and endothelium cells | [76] | |
mouse embryonic stem cells (MESCs) | curcumin | co-incubation | None | Mice | intranasal | astrocytes and neurons | [87] | |
multipotent mesenchymal stromal cells (MSCs) | miR-17-92 | transfection | None | Rats | intravenous | unknown | [166] | |
adipose-derived stem cells (ADSCs) | PEDF | transfection | None | Rats | intravenous | unknown | [170] | |
HEK-293T cells | recombinant human NGF mRNA | transfection | Lamp2b-RVG | Mice | intravenous | microglia, neurons, and astrocytes | [169] | |
bone marrow mesenchymal stem cells (BMSC) | miR-124 | electroporation | Lamp2b-RVG | Mice | intravenous | neurons, astrocytes, and oligodendrocytes | [165] | |
Repetitive mild traumatic brain injury (rmTBI) | microglia | miR-124-3p | transfection | None | Mice | intravenous | microglia, neurons, and astrocytes | [75] |
Spinal cord injury (SCI) | mesenchymal stem cells (MSC) | PTEN-siRNA | co-incubation | None | Rats | intranasal | neurons | [109] |
Multiple sclerosis | EL-4 cells | curcumin or JSI124 | co-incubation | None | Mice | intranasal | microglia | [175] |
mesenchymal stem cells (MSCs) | LJM-3064 aptamer | EDC/NHS | None | Mice | intravenous | unknown | [84] | |
Brain tumor | brain endothelial cell (bEND.3) | doxorubicin | co-incubation | None | zebrafishes | intravenous | unknown | [105] |
RAW264.7 | curcumin and SPIONs | electroporation | RGE-peptide | Mice | intravenous | glioma | [128] | |
ZIKV infection | HEK-293T cells | ZIKV-specific siRNA | electroporation | Lamp2b-RVG | Mice | intravenous | microglia, neurons, and astrocytes | [183] |
Morphine addiction | HEK-293T cells | Mu (MOR) siRNA | transfection | Lamp2b-RVG | Mice | intravenous | neuro2A | [182] |
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Share and Cite
Sun, K.; Zheng, X.; Jin, H.; Yu, F.; Zhao, W. Exosomes as CNS Drug Delivery Tools and Their Applications. Pharmaceutics 2022, 14, 2252. https://doi.org/10.3390/pharmaceutics14102252
Sun K, Zheng X, Jin H, Yu F, Zhao W. Exosomes as CNS Drug Delivery Tools and Their Applications. Pharmaceutics. 2022; 14(10):2252. https://doi.org/10.3390/pharmaceutics14102252
Chicago/Turabian StyleSun, Ke, Xue Zheng, Hongzhen Jin, Fan Yu, and Wei Zhao. 2022. "Exosomes as CNS Drug Delivery Tools and Their Applications" Pharmaceutics 14, no. 10: 2252. https://doi.org/10.3390/pharmaceutics14102252
APA StyleSun, K., Zheng, X., Jin, H., Yu, F., & Zhao, W. (2022). Exosomes as CNS Drug Delivery Tools and Their Applications. Pharmaceutics, 14(10), 2252. https://doi.org/10.3390/pharmaceutics14102252