Functional paclitaxel-manganese-doped mesoporous silica nanoparticles for orthotopic brain glioma targeted therapy

Abstract

Brain glioma is a highly comorbid tumor with high mortality. In this study, plasma complex component-functionalized manganese-doped mesoporous silica nanoparticles (PMMSN) were prepared and loaded with paclitaxel (PTX) by adsorption for brain glioma treatment. The nanodrug delivery system crossed the blood–brain barrier (BBB) and exhibited redox responsiveness and pH-sensitive release characteristics. In vivo imaging revealed the ability of the preparation to cross the BBB, and oxidative stress studies revealed the redox properties of the carrier material. The drug release data indicated that the amount of drug released from the drug-loaded samples (PMMSN-PTX) in medium at pH 5.0 was 84.1 ± 1.62 % after 10 h, whereas it was 53.7 ± 1.53 % in pH 7.4 medium after 24 h. These findings demonstrated that the drug was pH sensitive and released slowly. In vitro cell-based assays, including cellular uptake, flow cytometry, western blotting, and immunofluorescence staining, showed that PMMSN-PTX facilitated drug delivery across the BBB and promoted tumor cell apoptosis. These in vivo antitumor effects further demonstrated that it significantly inhibited tumor cell proliferation. We believe that PMMSN-PTX is a promising bionic nanosystem agent that could be used as a new agent for treating glioma.

Keywords

• Manganese-doped mesoporous silica nanoparticles
• Orthotopic brain glioma
• Paclitaxel
• Blood–brain barrier