GMT8 aptamer conjugated PEGylated Ag@Au core-shell nanoparticles as a novel radiosensitizer for targeted radiotherapy of glioma

Abstract

Radiotherapy is one of the main treatment modalities for glioma, but the therapeutic efficacy is often limited by the radioresistance of tumor cells. The radiosensitization effects of silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) on tumors have been confirmed by previous studies. To enhance the specific killing effect of irradiation on tumor cells, targeted modification of radiosensitizers is urgently needed. Herein, we developed polyethylene glycol (PEG)-coated Ag@Au core-shell nanoparticles (PSGNPs) modified with GMT8 aptamer (GSGNPs) and evaluated their radiosensitization effects on glioma cells through in vivo and in vitro experiments. Transmission electron microscope image showed that the prepared PSGNPs had a spherical core-shell structure with an average size of 11 nm. The ultraviolet-visible absorption spectra and Fourier transform infrared spectra displayed that GMT8 was successfully conjugated to PSGNPs. The results of dark-field imaging revealed that the targeting ability of GSGNPs to U87 glioma cells was much better than that to normal human microvascular endothelial cells. Additionally, it was also found that the endocytic pathways of GSGNPs mainly involved clathrin-mediated endocytosis and macropinocytosis. The sensitization enhancement ratio of GSGNPs was calculated to be 1.62, which was higher than that of PSGNPs. In vivo imaging results showed that GSGNPs exhibited good tumor targeting and retention capabilities, and the fluorescence intensity ratio of Cy5-GSGNPs to Cy5-PSGNPs reached a peak at 4 h after injection. More importantly, the median survival time of mice bearing U87 glioma was significantly prolonged after intravenous administration of GSGNPs combined with radiotherapy. This work demonstrated that GSGNPs could be used as an effective nano-radiosensitizer for targeted radiotherapy of glioma.