Tri-Block Copolymer Nanoparticles Modified with Folic Acid for Temozolomide Delivery in Glioblastoma.

In the present study, Folic Acid (FA) ligand was used to functionalize Temozolomide-loaded Poly (ethylene Glycol)-Poly (Butylene Adipate)-Poly (ethylene Glycol)-coated magnetite nanoparticles (TMZ-SPION-PEG-PBA-PEG) for targeted chemotherapy of glioma cells. Four types of nanoparticles were synthesized with the hydrodynamic diameters of 24-49 nm. Using MTT, Prussian blue, and ICP-OES assays, the cytotoxicity effect and cellular uptake of nanoparticles were evaluated in C6 cancer cells and OLN-93 normal cells. Moreover, in vitro anti-tumor efficacy of nanoparticles was evaluated through colony formation, quantitative real-time PCR, and flow cytometry analysis. As compared to OLN-93 cells TMZ-SPION-PEG-PBA-PEG-FA nanoparticles showed an increase in the cytotoxicity of the loaded TMZ in C6 cells within 24 and 48 h treatment (P < 0.0001), while such effect was not observed in the case of non-targeting nanoparticles. The colony formation, flow cytometry, and real-time PCR assays showed that TMZ-SPION-PEG-PBA-PEG-FA led to the enhancement of inhibitory effects to C6 cells compared to TMZ alone (P < 0.05). These results suggested that TMZ-SPION-PEG-PBA-PEG-FA could effectively slow down cell proliferation, due to the targeting effect and the high accumulation of TMZ in C6 cells via an FA-receptor mediated endocytosis. In conclusion, TMZ-loaded magnetite FA-conjugated PEG-PBA-PEG NPs could be used as a targeted drug delivery system for targeted therapy of brain glioma.