期刊
MOLECULAR PHARMACEUTICS
卷 -, 期 -, 页码 -出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.2c00755
关键词
blood-brain barrier; cell-penetrating peptide; drug delivery; glioblastoma; mesoporous silica nanoparticle; pharmacokinetic
The blood-brain barrier is a protective barrier that prevents potential damages to the brain from chemicals in the bloodstream. This study showed that modifying mesoporous silica nanoparticles with TAT peptide improves the penetration of methotrexate into the brain. The results suggest that this nanosystem could be a promising drug carrier to overcome the blood-brain barrier and deliver methotrexate into the brain.
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 trans activator of transcription (TAT) peptide, a cell-penetrating peptide, to produce MSNNH-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.
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