Abstract
Glioblastoma is considered the most fatal malignant brain tumor that starts from the central nervous system (CNS), where the blood-brain barrier (BBB) remains the biggest challenge for active targeting of drugs in malignant brain tumor. Thereby, we have designed a paclitaxel PTX@ANG/FA-NPs hybrid novel nanodrug delivery system that can overcome the clinical BBB. The structural and morphological characterization of PTX@ANG/FA-NPs confirmed successful synthesis of nanomicelles with the size range of about 160 to 170 nm. The overall repressive effect of PTX@ANG/FA-NPs on human glioblastoma U251 cells was 1.2-times that of PTX alone. In vitro cellular uptake assay also demonstrated that the dual-targeted nanoparticles (NPs) were more easily taken up by glioblastoma U251 cells. Although the antiglioblastoma activity was confirmed by cell migration assay, apoptosis assay, and cellular uptake assay, the absorption was studied by in vivo fluorescence imaging and brain distribution. The synthesized PTX@ANG/FA-NPs probe significantly inhibited the migration of U251 within the cells and promoted the apoptosis process. Moreover, the RhB@ANG/FA-NPs and PTX@ANG/FA-NPs showed higher accumulating potential at sites of tumor BBB disruption. The novel nanodrug delivery system mediated enhanced distribution of drugs at the targeted site for therapeutics efficacies against glioblastomas across the BBB.
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