Nucleolin-targeted selenium nanocomposites with enhanced theranostic efficacy to antagonize glioblastoma

Abstract

Glioblastoma is considered as the most lethal cancer, due to the inability of chemotherapeutic agents to reach the glioma core as well as the infiltration zone of the invasive glioma cells. Nanotechnology based delivery systems bring new hope to cancer targeted therapy and diagnosis owing to their enhancement of selective cellular uptake and cytotoxicity to cancer cells through various smart designs. We prepared a novel selenium-based composite nanosystem (QDs/Se@Ru(A)) surface functionalized with the AS1411 aptamer and loaded with quantum dots to realize selectivity against glioblastoma and enhance theranostic effects. This cancer targeted nanosystem significantly enhanced the cellular uptake in glioma cells through nucleolin mediated endocytosis, and increased selectivity between cancer and normal cells. The QDs/Se@Ru(A) nanosystem can also be used for spontaneous fluorescence of biological probes to explore their localization in cancer cells, because of the green fluorescent quantum dots loaded into the selenium nanoparticles. QDs/Se@Ru(A) promotes excess reactive oxygen species (ROS) production in glioma cells to induce DNA damage, thus activating diverse downstream signaling pathways, and inhibiting proliferation of U87 cells through the G2/M phase cycle. Thus, this study provides an effective strategy to design a theranostic agent to simultaneously realize cell imaging and therapy for glioblastoma treatment.