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Enhancing Methotrexate Delivery in the Brain by Mesoporous Silica Nanoparticles Functionalized with Cell-Penetrating Peptide using in Vivo and ex Vivo Monitoring

Shadmani, Nasim, Makvandi, Pooyan, Parsa, Maliheh, Azadi, Amir, Nedaei, Keivan, Mozafari, Negin, Poursina, Narges, Mattoli, Virgilio, Tay, Franklin R., Maleki, Aziz, Hamidi, Mehrdad·2023·Molecular Pharmaceutics
DOI 10.1021/acs.molpharmaceut.2c00755
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Abstract

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 N 2 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 bra…

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Metadata

Authors
Shadmani, N., Makvandi, P., Parsa, M., Azadi, A., Nedaei, K., Mozafari, N., Poursina, N., Mattoli, V., Tay, F. R., Maleki, A., & Hamidi, M.
Venue
Molecular Pharmaceutics
Publisher
American Chemical Society (ACS)
Published
2023-02-10
Volume
20
Issue
3
Pages
1531-1548
ISSN
  • 1543-8384
  • 1543-8392
DOI
10.1021/acs.molpharmaceut.2c00755
Cited by
48
References
2
Language
en
Licence
Funders
  • Iran National Science Foundation (95004483)
  • Zanjan Pharmaceutical Nanotechnology Research Center (A-12-233-19)

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