Abstract
A very important cause of the frustration with drug therapy for central nervous system (CNS) diseases is the failure of drug delivery. The blood–brain barrier (BBB) prevents most therapeutic molecules from entering the brain while maintaining CNS homeostasis. Scientists are keen to develop new brain drug delivery systems to solve this dilemma. Extracellular vesicles (EVs), as a class of naturally derived nanoscale vesicles, have been extensively studied in drug delivery due to their superior properties. This review will briefly present current brain drug delivery strategies, including invasive and non-invasive techniques that target the brain, and the application of nanocarriers developed for brain drug delivery in recent years, especially EVs. The cellular origin of EVs affects the surface protein, size, yield, luminal composition, and other properties of EVs, which are also crucial in determining whether EVs are useful as drug carriers. Stem cell-derived EVs, which inherit the properties of parental cells and avoid the drawbacks of cell therapy, have always been favored by researchers. Thus, in this review, we will focus on the application of stem cell-derived EVs for drug delivery in the CNS. Various nucleic acids, proteins, and small-molecule drugs are loaded into EVs with or without modification and undergo targeted delivery to the brain to achieve their therapeutic effects. In addition, the challenges facing the clinical application of EVs as drug carriers will also be discussed. The directions of future efforts may be to improve drug loading efficiency and precise targeting.
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Abbreviations
- AD:
-
Alzheimer’s disease
- ADMSCs:
-
Adipose-derived mesenchymal stem cells
- ADSCs:
-
Adipose-derived stem cells
- AMT:
-
Adsorptive-mediated transcytosis
- Axin2:
-
Axis inhibition protein 2
- Aβ:
-
β-Amyloid
- BBB:
-
Blood-brain barrier
- BECs:
-
Brain endothelial cells
- BMSCs:
-
Bone marrow mesenchymal stem cells
- CCL-2:
-
C-C chemokine ligand 2
- CCR-2:
-
C-C chemokine receptor type 2
- CED:
-
Convection enhanced delivery
- CMT:
-
Carrier-mediated transport
- CNS:
-
Central nervous system
- CPP:
-
Cell-penetrating peptide
- CXCR4:
-
CXC motif chemokine receptor type 4
- DALYs:
-
Disability-adjusted life-years
- DLS:
-
Dynamic light scattering
- ECs:
-
Endothelial cells
- EPCs:
-
Endothelial progenitor cells
- ESCs:
-
Embryonic stem cells
- EVs:
-
Extracellular vesicles
- 5-FC:
-
5-Fluorocytosine
- FDA:
-
US Food and Drug Administration
- FUS:
-
Focused ultrasound
- GBM:
-
Glioblastoma multiforme
- GCV:
-
Ganciclovir
- GSCs:
-
Glioma stem cells
- HD:
-
Huntington’s disease
- hiPSCs:
-
Human induced pluripotent stem cells
- HMOX1:
-
Heme oxygenase-1
- HSCs:
-
Hematopoietic stem cells
- HSSP:
-
HMOX1-specific short peptide
- HSVTK:
-
Herpes simplex virus thymidine kinase
- HTT:
-
Huntingtin
- iPSCs:
-
Induced pluripotent stem cells
- ISEV:
-
International Society for Extracellular Vesicles
- MCAO:
-
Middle cerebral artery occlusion
- MPS:
-
Mononuclear phagocytic system
- MRgFUS:
-
Magnetic resonant–guided focused ultrasound
- MSCs:
-
Mesenchymal stem cells
- MSC-EVs:
-
MSC-derived EVs
- MT:
-
Mechanical thrombectomy
- NFT:
-
Neurofibrillary tangles
- NLCs:
-
Nanostructured lipid carriers
- NPs:
-
Nanoparticles
- NSCs:
-
Neural stem cells
- NTA:
-
Nanoparticle tracking analysis
- PBCA:
-
Poly(butylcyanoacrylate)
- PD:
-
Parkinson’s disease
- PEDF:
-
Pigment epithelium-derived factor
- PEG:
-
Polyethylene glycol
- PLGA:
-
Poly(lactic-co-glycolic acid)
- PNPs:
-
Polymeric nanoparticles
- PSCI:
-
Post-stroke cognitive impairment
- PTX:
-
Paclitaxel
- RMT:
-
Receptor-mediated transcytosis
- RVG:
-
Rabies virus glycoprotein
- SCs:
-
Stem cells
- SEC:
-
Size exclusion chromatography
- sEVs:
-
Small extracellular vesicles
- siRNA:
-
Small interfering RNA
- SPION:
-
Superparamagnetic iron oxide nanoparticles
- TfR:
-
Transferrin receptor
- TJ:
-
Tight junction
- TMZ:
-
Temozolomide
- tPAs:
-
Tissue plasminogen activators
- yCD::UPRT:
-
Yeast cytosine deaminase (CD)::uracil phosphoribosyl transferase fusion gene
- Zeb2:
-
Zinc finger E-box binding homeobox 2 protein
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (No. 81774059), the Tianjin Natural Science Foundation (No. 19JCZDJC37100)
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National Natural Science Foundation of China (No. 81774059); Tianjin Natural Science Foundation (No. 19JCZDJC37100).
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All authors contributed to the study conception and design. Yuying Guo, Dongsheng Hu and Mingli Li performed the literature search. The first draft of the manuscript was written by Yuying Guo and Dongsheng Hu. Lu Lian, Linna Zhao and Yuying Guo drew the figures. Shixin Xu and Huijing Bao critically revised the work. All authors read and approved the final manuscript.
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Guo, Y., Hu, D., Lian, L. et al. Stem Cell-derived Extracellular Vesicles: A Promising Nano Delivery Platform to the Brain?. Stem Cell Rev and Rep 19, 285–308 (2023). https://doi.org/10.1007/s12015-022-10455-4
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DOI: https://doi.org/10.1007/s12015-022-10455-4