Methotrexate (MTX), an analog of folic acid (FA), is a drug widely used in cancer treatment. To prevent its potential toxicity and enhance therapeutic efficacy, targeted drug delivery systems, especially nanotechnology-folate platforms, are a central strategy. Gold nanoparticles (AuNPs) are promising candidates to be used as drug delivery systems because of their small particle sizes and their inertness for the body. In this study, glutathione (GSH)-coated FA-modified spherical AuNPs (5.6 nm) were successfully synthesized, and the anticancer activity of novel MTX-loaded (MTX/Au-GSH-FA) NPs (11 nm) was examined. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) results showed that MTX/AuNPs possess spherical morphology, nanoscaled particle size, narrow size distribution, and good stability. In vitro studies showed that cytotoxicity of MTX/Au-GSH-FA to folate receptor-positive (FR+) human brain (U-87 MG) and cervical (HeLa) cancer cells enhanced significantly (∼3 and ∼10 fold, respectively) compared to free MTX while there was no significant effect in FR−negative human cell lines A549 (lung carcinoma), PC3 (prostate carcinoma), HEK-293 (healthy embryonic kidney). Moreover, the receptor specificity of the conjugate was shown by fluorescent microscopic imaging. In conclusion, these results indicate that the synthesized novel MTX/Au-GSH-FA NP complex seems to be a good candidate for effective and targeted delivery in FR+ cancer therapy.
Pentylenetetrazole (PTZ)-induced kindling is an animal model for studying human temporal lobe epilepsy (TLE), which is characterized by alterations of hippocampal neurons and memory. Although the intranasal (IN) administration of oxytocin (OT) has limited efficiency, nanoparticles (NPs) are a promising candidate to deliver OT to the brain. However, there are very limited data on epilepsy research about oxytocin-loaded nanoparticles (NP-OTs). The aim of this study is to investigate the effects of IN administration of chronic NP-OTs on the hippocampus of PTZinduced male epileptic rats in terms of seizure severity, memory, neurogenesis, and neuronal damage. Saline/OT/NP-OTs were administrated to both control (Ctrl) and PTZ groups intranasally. Consequently, saline and PTZ were injected, respectively, 25 times every 48 h. Then, seizure severity (score and latency) was calculated for the PTZ groups. A spatial working memory evaluation test (SWMET) was performed after the last injection. Hippocampus histopathology, neurogenesis, and apoptosis were demonstrated. Serum total antioxidant status (TAS) and total oxidant status (TOS) levels and the oxidative stress index (OSI) were measured. We showed that OTs and NP-OTs prevented the kindling development and had positive effects on seizure severity. SWMET-related behaviors were also recovered in the PTZ + NP-OT group. A significant increase of neurogenesis and decrease of apoptosis in the hippocampus of the PTZ + NP-OT group were observed, while OTs and NP-OTs had protective effects against PTZ-induced damage to hippocampal neurons. Our results indicate that the chronic administration of NP-OTs may have positive effects on hippocampal damage via increasing neurogenesis and decreasing apoptosis and seizure severity.
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