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Topics in Current Chemistry (2020) 378:15
of the tumor growth, and, when combined with photothermal therapy, the results
showed a more effective treatment.
4.2.2 Neurodegeneration Treatment
One of the big problems in the treatment of neurodegenerative diseases like Parkinson, dementia, or Alzheimer’s, is the presence of the blood–brain barrier (BBB).
The BBB restricts the passage of bacteria and toxic molecules to avoid brain damage
but also prevents the brain uptake of most pharmaceuticals, precluding the pass of
drugs from blood circulation to brain tissue. In fact, neurological disorders belong
to the group of pathologies with the greatest need of new technologies to improve
diagnosis and provide an adequate therapy, and nanobiotechnology can help in both.
Al-Jamal’s laboratory proved [179–181] that CNTs are able to cross the
blood–brain barrier without damaging it. They used in vitro cultures of primary
porcine brain endothelial cells, which simulate the BBB, showing that MWCNTs
functionalized with NH 3 crossed 13% of the layer in 72 h. They also demonstrated
in vivo that 5 min after intravenous injection of MWCNTs-NH 3 in mice, 1% of the
injected dose crossed the BBB. In further experiments, they studied the impact of the
diameter of the nanotube and the functionalization with angiopep-2 (AGP), a ligand
for the low-density lipoprotein receptor related protein-1, in the extent of passing
the BBB. They found that wider nanotubes linked with AGP showed a higher effect
on crossing the BBB than those not functionalized. Thinner CNTs did not depict
any improvement in the brain uptake between functionalized and unfunctionalized MWCNTs, although they exhibited more uptake than the wider ones. Finally,
they tested them in vivo using a GL261 glioma model, showing higher uptake for
CNT functionalized with AGP. Costa et al. [182] took advantage of this property to
develop an Alzheimer’s biomarker based on gadolinium. MWCNTs were functionalized with the Pittsburgh Compound B, a molecule that binds to the amyloid beta
plaques present in Alzheimer’s disease and is currently used for imaging Alzheimer’s with PET. The group studied the in vivo distribution of the nanotubes, finding
that they were able to cross the BBB, making them a good contrast agent to detect
the presence of the plaques with MRI. Lohan et al. [183] reported the development
of MWCNTs functionalized with berberine (BRB), an isoquinoline alkaloid used in
dementia and other mental disorders, to evaluate the anti-Alzheimer’s potential of
the drug. The authors injected the nanotubes in healthy male Wistar rats after intracerebroventricular administration of amyloid beta peptide. They proved that BRBMWCNTS crossed the BBB, reaching the plaques, and found a decrease of malondialdehyde and reduced glutathione, two of Alzheimer’s biomarkers.
The structural damage occurring in some neuro-diseases can also be minimized
with carbon nanotubes. Hassanzadeh et al. [184] prepared MWCNTs-NGF complexed with nerve growth factor (NGF), a protein related to the survival and maintenance of neurons population, and investigated its effect in an in vitro model of
ischemia. The results were compared with those obtained with free NGF, finding
higher protection for the new CNT-NGF complex.
As in cancer, CNTs found further applications in neurodegenerative diseases
beyond drug delivery. CNTs can be used to activate brain cells due to their electrical
199
Reprinted from the journal
Topics in Current Chemistry (2020) 378:15
of the tumor growth, and, when combined with photothermal therapy, the results
showed a more effective treatment.
4.2.2 Neurodegeneration Treatment
One of the big problems in the treatment of neurodegenerative diseases like Parkinson, dementia, or Alzheimer’s, is the presence of the blood–brain barrier (BBB).
The BBB restricts the passage of bacteria and toxic molecules to avoid brain damage
but also prevents the brain uptake of most pharmaceuticals, precluding the pass of
drugs from blood circulation to brain tissue. In fact, neurological disorders belong
to the group of pathologies with the greatest need of new technologies to improve
diagnosis and provide an adequate therapy, and nanobiotechnology can help in both.
Al-Jamal’s laboratory proved [179–181] that CNTs are able to cross the
blood–brain barrier without damaging it. They used in vitro cultures of primary
porcine brain endothelial cells, which simulate the BBB, showing that MWCNTs
functionalized with NH 3 crossed 13% of the layer in 72 h. They also demonstrated
in vivo that 5 min after intravenous injection of MWCNTs-NH 3 in mice, 1% of the
injected dose crossed the BBB. In further experiments, they studied the impact of the
diameter of the nanotube and the functionalization with angiopep-2 (AGP), a ligand
for the low-density lipoprotein receptor related protein-1, in the extent of passing
the BBB. They found that wider nanotubes linked with AGP showed a higher effect
on crossing the BBB than those not functionalized. Thinner CNTs did not depict
any improvement in the brain uptake between functionalized and unfunctionalized MWCNTs, although they exhibited more uptake than the wider ones. Finally,
they tested them in vivo using a GL261 glioma model, showing higher uptake for
CNT functionalized with AGP. Costa et al. [182] took advantage of this property to
develop an Alzheimer’s biomarker based on gadolinium. MWCNTs were functionalized with the Pittsburgh Compound B, a molecule that binds to the amyloid beta
plaques present in Alzheimer’s disease and is currently used for imaging Alzheimer’s with PET. The group studied the in vivo distribution of the nanotubes, finding
that they were able to cross the BBB, making them a good contrast agent to detect
the presence of the plaques with MRI. Lohan et al. [183] reported the development
of MWCNTs functionalized with berberine (BRB), an isoquinoline alkaloid used in
dementia and other mental disorders, to evaluate the anti-Alzheimer’s potential of
the drug. The authors injected the nanotubes in healthy male Wistar rats after intracerebroventricular administration of amyloid beta peptide. They proved that BRBMWCNTS crossed the BBB, reaching the plaques, and found a decrease of malondialdehyde and reduced glutathione, two of Alzheimer’s biomarkers.
The structural damage occurring in some neuro-diseases can also be minimized
with carbon nanotubes. Hassanzadeh et al. [184] prepared MWCNTs-NGF complexed with nerve growth factor (NGF), a protein related to the survival and maintenance of neurons population, and investigated its effect in an in vitro model of
ischemia. The results were compared with those obtained with free NGF, finding
higher protection for the new CNT-NGF complex.
As in cancer, CNTs found further applications in neurodegenerative diseases
beyond drug delivery. CNTs can be used to activate brain cells due to their electrical
199
Reprinted from the journal