Abstract
The therapeutic modalities for glioblastoma multiforme fail badly due to the limitations of poor penetration through the blood-brain barrier and the lack of tumor targeting. In this study, we synthesized a neuropeptide (ANGIOPEP-2)-functionalized gold nanorod (GNR-ANGI-2) and systemically evaluated the cellular uptake and photothermal effects enhanced by the neuropeptide functionalization of the gold nanorod under laser or sham exposure. The expression of LRP1, the specific ligand for ANGIOPEP-2, was the highest in C6 cells among five studied glioma cell lines. The cellular internalization studies showed higher uptake of gold nanorods functionalized with ANGIOPEP-2 than of those functionalized with scrambled ANGIOPEP-2. The in vitro photothermal studies of C6 cells treated with GNR-ANGI-2 and laser showed a higher rate of apoptosis at early and late stages than cells treated with GNR-ANGI-2 without laser. Correspondingly, in vitro ROS evaluation showed a higher intensity of ROS production in cells treated with GNR-ANGI-2 under laser irradiation. The Western blotting results indicated that GNR-ANGI-2 with laser exposure activated the caspase pathway of apoptosis, and GNR-ANGI-2 with sham exposure induced autophagy in C6 cells. The current study provides in-depth knowledge on the effective time point for maximum cellular uptake of GNR-ANGI-2 to achieve a better anti-glioma effect. Moreover, by exploring the molecular mechanism of cell death with GNR-ANGI-2-mediated photothermal therapy, we could modify the nanoshuttle with multimodal targets to achieve more efficient anti-glioma therapy in the future.