| Glioma is a most common neoplasm of the central nervous system,with highest mortality rate.On the basis of their histological appearance,they have been traditionally classified as astrocytic,oligodendroglial or ependymal tumors and assigned WHO grades I–IV,which indicate different degrees of malignancy.Tremendous progress in genomic,transcriptomic and epigenetic profiling has resulted in new concepts of classifying and treating gliomas.Glioma harbors glioma stem cells(GSCs)that not only initiate and maintain malignant growth but also promote therapeutic resistance including Temozolomide(TMZ)and radiotherapy resistance.Thus,targeting GSCs is critical for overcoming the resistance to improve glioma treatment.The Present study was designed to examine the therapeutic effect of Iguratimod(IGU)encapsulated-PLGA nanoparticles(IGU-PLGA-NPs),which showed inhibition of glioma cells proliferation both in vitro and in vivo.IGU was encapsulated in PLGA nanoparticles with an average size of 100-200 nm were prepared using modified doubleemulsion(W1/O/W2)method.CCK-8 analysis of Glioma cancer cells(U87,U118,and U251)and glioma stem-like cells(GSCs)(U87Sc,U118 Sc,and U251Sc),demonstrated significant inhibition of their growth treated with IGU-PLGA-NPs.IGU-PLGA-NPs inhibits migration in glioma cells as well as tumor sphere formation in GSCs.Treatment with IGU-PLGA-NPs showed significant decrease in tumor growth through the apoptotic pathway in mice model without any visible organ toxicity and it can successfully cross the blood brain barrier(BBB).Most Importantly,IGU-PLGA NPs also inhibits the PI3K/AKT signaling pathway via activation of PTEN and induces apoptosis in TMZ-resistant glioma.Our intriguing results revealed the first experimental evidence for the anticancer effect of IGU-PLGA-NPs against glioma and TMZ-resistant glioma in vitro and also in vivo. |
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