Metal–Organic Frameworks for Overcoming the Blood–Brain Barrier in the Treatment of Brain Diseases: A Review
Abstract
:1. Introduction
2. Synthesis and Characterization of MOFs
3. Drug Loading and Drug Release in MOFs
4. MOFs in the Treatment of Brain Diseases
5. MOFs in the Treatment of Glioblastoma Multiforme
6. MOFs in the Treatment of Parkinson
7. MOFs in the Treatment of Alzheimer’s
8. MOFs in the Treatment of Stroke
9. Challenges in Developing MOFs for Treating Brain Diseases
10. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
5-FU | 5-Fluorouracil |
Aβ | Amyloid β |
AIC | 5-Aminoimidazole-4-carboxamide |
AD | Alzheimer’s disease |
AFM | Atomic force microscopy |
ALS | Amyotrophic lateral sclerosis |
AuNPs | Gold nanoparticles |
BCMD | BSO-CAT@MOF-199@DDM |
BET | Brunauer–Emmett–Teller |
BSO | Buthionine-sulfoximine |
CBD | Cannabidiol |
Ca-MOFs | Calcium-based MOFs |
CD | Circular dichroism |
CD-MOFs | Cyclodextrin-based MOFs |
CeO2 | Cerium dioxide |
CCM | Curcumin |
DSC | Differential scanning calorimetry |
DOX | Doxorubicin |
Defluorinated MK6240, DMK6240 | 5-Amino-3-(pyrrolo [2,3-c]pyridin-1-yl)isoquinoline |
FeCl3 | Fe3+ ions |
Fe-TCPP | Fe-5,10,15,20-tetra (4-carboxyphenyl) porphyrin |
FBF | Fenbufen |
GFP-PSD95 | PSD95 interacted with green fluorescent protein |
GA | L-glutamic acid |
GA | Gallic acid |
GBM | Glioblastoma multiforme |
ICD | Immunogenic cell death |
ICP-MS | Inductively coupled plasma mass spectrometry |
IR | Infrared |
MDA | Malondialdehyde |
MB | Methylene blue |
MNPs | Magnetic nanoparticles |
MOFs | Metal–organic frameworks |
MMOF | Multifunctional MOF |
MTIC | 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide |
MTX | Methotrexate |
NIR | Near-infrared |
NO | Nitric oxide |
NPs | Nanoparticles |
NMDARs | N-methyl-D-aspartate receptors |
NOTA | 1,4,7-triazacyclononane-1,4,7-triacetic acid |
OA | Okadaic acid |
OXA | Oxaliplatin |
PB | Prussian blue |
PCN | Porous coordination network |
PCN−222@ICG | Porphyrinic MOF and indocyanine green nanoprobe |
PBS | Phosphate-buffered saline |
Ptzymes | Platinum nanozymes |
QCT | Quercetin |
RB | Rose bengal |
ROS | Reactive oxygen species |
RVG | Rabies virus glycoprotein |
SCXRD | Single crystal X-ray diffraction |
SEM | Scanning electron microscopy |
TEM | Transmission electron microscopy |
TGA | Thermogravimetric analysis |
TCPP | Tetra-kis(4-carboxyphenyl)porphyrin |
ThT | Thioflavin T |
TMZ | Temozolomide |
XPS | X-ray photoelectron spectroscopy |
XP | X-ray photoelectron spectroscopy |
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Delivery System | Advantages | Disadvantages |
---|---|---|
MOFs | High surface area and porosity for high drug loading; tunable pore size; easy functionalization; potential for targeted delivery; high drug loading capacity; protective encapsulation; versatility; low density; structural diversity | Potential for premature drug release; challenges in scalability and cost-effectiveness in clinical settings; difficulty in targeting; stability issues under certain conditions; limited biocompatibility |
Liposomes | Biocompatibility and biodegradability; versatility in drug encapsulation; ability to encapsulate both hydrophilic and hydrophobic drugs; reduced toxicity; flexibility in size and surface modification; enhanced permeability and retention effect; potential for targeted delivery; protection of drugs; relatively low immunogenicity | Instability; potential for drug leakage; relatively lower drug loading capacity; high production costs; limited penetration; complex preparation; difficulty in controlling/sustaining drug release |
Micelles | Good for solubilizing hydrophobic drugs; good biocompatibility; ease of preparation; enhanced permeability and retention effect; ability to enhance drug solubility; long circulation time; potential for targeted delivery; low toxicity; stimulus responsiveness; minimal size; self-assembly | Lower drug loading capacity compared to other systems; potential for premature drug release; difficulty in controlling release rates; challenges in large-scale production; poor solubility; low loading capacity; undesirable physical stability |
Nanoparticles | Good stability; controlled drug release; good; large surface area; biocompatibility; high drug loading capacity; versatility in drug delivery; enhanced drug solubility; targeted delivery; ability to cross blood–brain barrier; facile synthesis; easy surface decoration; ultra-small sizes | Burst release; rapid elimination; potential toxicity; processes; high production costs; potential for aggregation; poor degradability; low solubility; immunogenicity |
MOF System | Drug Delivered | How to Overcome BBB | Disease Type | Therapeutic Efficiency | Ref. |
---|---|---|---|---|---|
MILB@LR | Oxaliplatin (OXA) | RABV-mimetic design with RVG29 peptide for BBB penetration and targeting GBM cells | GBM | Effective brain tumor penetration, significant tumor growth inhibition | [59] |
BSO-CAT@MOF-199@DDM (BCMD) | Cu2+ Ions, Buthionine-Sulfoximine (BSO), Catalase (CAT) | Intranasal administration for direct brain tumor delivery | GBM | Induced cuproptosis, enhanced immune response, improved therapeutic efficacy with immune checkpoint blockade | [61] |
MNPs@MIL-101(Fe) | Temozolomide (TMZ) | Integration of MIL frameworks with Fe3O4 magnetic nanoparticles for improved BBB penetration | GBM | Enhanced drug loading and release, increased cytotoxicity against GBM cells | [62] |
CBD/Mg-GA MOF | Cannabidiol (CBD), Gallic Acid (GA) | Increased permeability (pH-sensitive degradation) | GBM | Significant increase in cell death and reduced colony formation, improved antioxidant activity | [63] |
ZIF-8@PB-QCT | Quercetin (QCT) | NIR light activation to enhance BBB permeability | PD | Improved mitochondrial function, reduced PD symptoms in mice, enhanced motor function | [64] |
Ptzyme@D-ZIF | Nanozymes (Ptzymes) | Enhanced BBB accumulation through clathrin- and caveolae-mediated endocytosis | PD | Reduced neuroinflammation, improved behavioral and pathological outcomes, superior ROS scavenging | [65] |
MOF@Man Liposome | Fe-TCPP, Zr6 Clusters | Mannitol-coated liposomes for BBB permeability | PD | Enhanced motor function, memory, and gene normalization in mice | [66] |
AuNPs@PEG@MIL-101 | Amyloid β Binder | Direct interaction with Aβ monomers and fibrils | AD | Inhibited Aβ aggregation, protected PC12 cells from Aβ-induced damage, reduced ROS values | [67] |
Fe-MIL-88B-NH2-NOTA-DMK6240/MB | Methylene Blue | Functionalized with NOTA and DMK6240 for targeting tau proteins | AD | Inhibited tau protein aggregation, reduced neuronal death, improved cognitive function | [68] |
PCN-224 | Singlet Oxygen | NIR light activation for photooxygenation | AD | Prevented Aβ aggregation, reduced Aβ-induced cytotoxicity, enhanced singlet oxygen production | [69] |
TR-ZRA | CD22 shRNA, Aβ Aptamers, Chlorogenic Acid | Erythrocyte membrane camouflaging for BBB crossing and Aβ plaque monitoring | AD | Reduced Aβ burden, improved microglial phagocytosis, enhanced memory function | [70] |
PCN−222@ICG | Indocyanine Green | RVG peptide modification for BBB penetration | AD | Reduced Aβ plaque density and size, enhanced therapeutic efficacy | [71] |
Ca-MOF@miR-124 | MicroRNA-124 (miR-124) | Nano delivery system for improved stability and internalization | Ischemic Stroke | Increased neuronal differentiation, reduced infarct size in mice, improved neuronal survival | [72] |
CeO2@ZIF-8 | CeO2 | Lysosome-mediated endocytosis | Ischemic Stroke | Reduced oxidative stress and infarct size, improved neurological outcomes | [74] |
PSD95-nNOS/Fe-MOF | PSD95-nNOS Uncouplers | Magnetic Fe-MOFs for screening uncouplers | Ischemic Stroke | High-throughput screening for PSD95-nNOS uncouplers | [76] |
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Nabipour, H.; Rohani, S. Metal–Organic Frameworks for Overcoming the Blood–Brain Barrier in the Treatment of Brain Diseases: A Review. Nanomaterials 2024, 14, 1379. https://doi.org/10.3390/nano14171379
Nabipour H, Rohani S. Metal–Organic Frameworks for Overcoming the Blood–Brain Barrier in the Treatment of Brain Diseases: A Review. Nanomaterials. 2024; 14(17):1379. https://doi.org/10.3390/nano14171379
Chicago/Turabian StyleNabipour, Hafezeh, and Sohrab Rohani. 2024. "Metal–Organic Frameworks for Overcoming the Blood–Brain Barrier in the Treatment of Brain Diseases: A Review" Nanomaterials 14, no. 17: 1379. https://doi.org/10.3390/nano14171379