TY - JOUR
T1 - Enhancing Methotrexate Delivery in the Brain by Mesoporous Silica Nanoparticles Functionalized with Cell-Penetrating Peptide using in Vivo and ex Vivo Monitoring
AU - Shadmani, Nasim
AU - Makvandi, Pooyan
AU - Parsa, Maliheh
AU - Azadi, Amir
AU - Nedaei, Keivan
AU - Mozafari, Negin
AU - Poursina, Narges
AU - Mattoli, Virgilio
AU - Tay, Franklin R.
AU - Maleki, Aziz
AU - Hamidi, Mehrdad
N1 - Publisher Copyright:
© 2023 American Chemical Society.
PY - 2023/3/6
Y1 - 2023/3/6
N2 - The blood-brain barrier (BBB) acts as a physical/biochemical barrier that protects brain parenchyma from potential hazards exerted by different xenobiotics found in the systemic circulation. This barrier is created by “a lipophilic gate” as well as a series of highly organized influx/efflux mechanisms. The BBB bottleneck adversely affects the efficacy of chemotherapeutic agents in treating different CNS malignancies such as glioblastoma, an aggressive type of cancer affecting the brain. In the present study, mesoporous silica nanoparticles (MSNs) were conjugated with the transactivator of transcription (TAT) peptide, a cell-penetrating peptide, to produce MSN-NH-TAT with the aim of improving methotrexate (MTX) penetration into the brain. The TAT-modified nanosystem was characterized by Fourier transform infrared spectrometry (FTIR), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light scattering (DLS), and N2 adsorption-desorption analysis. In vitro hemolysis and cell viability studies confirmed the biocompatibility of the MSN-based nanocarriers. In addition, in vivo studies showed that the MTX-loaded MSN-NH-TAT improved brain-to-plasma concentration ratio, brain uptake clearance, and the drug’s blood terminal half-life, compared with the use of free MTX. Taken together, the results of the present study indicate that MSN functionalization with TAT is crucial for delivery of MTX into the brain. The present nanosystem represents a promising alternative drug carrier to deliver MTX into the brain via overcoming the BBB.
AB - The blood-brain barrier (BBB) acts as a physical/biochemical barrier that protects brain parenchyma from potential hazards exerted by different xenobiotics found in the systemic circulation. This barrier is created by “a lipophilic gate” as well as a series of highly organized influx/efflux mechanisms. The BBB bottleneck adversely affects the efficacy of chemotherapeutic agents in treating different CNS malignancies such as glioblastoma, an aggressive type of cancer affecting the brain. In the present study, mesoporous silica nanoparticles (MSNs) were conjugated with the transactivator of transcription (TAT) peptide, a cell-penetrating peptide, to produce MSN-NH-TAT with the aim of improving methotrexate (MTX) penetration into the brain. The TAT-modified nanosystem was characterized by Fourier transform infrared spectrometry (FTIR), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light scattering (DLS), and N2 adsorption-desorption analysis. In vitro hemolysis and cell viability studies confirmed the biocompatibility of the MSN-based nanocarriers. In addition, in vivo studies showed that the MTX-loaded MSN-NH-TAT improved brain-to-plasma concentration ratio, brain uptake clearance, and the drug’s blood terminal half-life, compared with the use of free MTX. Taken together, the results of the present study indicate that MSN functionalization with TAT is crucial for delivery of MTX into the brain. The present nanosystem represents a promising alternative drug carrier to deliver MTX into the brain via overcoming the BBB.
KW - blood−brain barrier
KW - cell-penetrating peptide
KW - drug delivery
KW - glioblastoma
KW - mesoporous silica nanoparticle
KW - pharmacokinetic
UR - http://www.scopus.com/inward/record.url?scp=85148039868&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85148039868&partnerID=8YFLogxK
U2 - 10.1021/acs.molpharmaceut.2c00755
DO - 10.1021/acs.molpharmaceut.2c00755
M3 - Article
C2 - 36763486
AN - SCOPUS:85148039868
SN - 1543-8384
VL - 20
SP - 1531
EP - 1548
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
IS - 3
ER -
