25^th Nano Congress for Future Advancements

Biography

Biography: Samaneh kabirian Dehkordi

Abstract

AS1411 is a G-rich oligodeoxynucleotide aptamer that has been used in phase II clinical trials for the potential treatment of cancers. Forming a G-quartet structure, AS1411 binds to cell surface nucleolin specifically, and is subsequently internalized into the tumor cell. It remains unclear how AS1411 binding to nucleolin leads to cell proliferation inhibition and cell death. Despite remarkable AS1411 results in a few patients, the overall rate of response has been low, possibly because it has less than optimal pharmacology and relatively low potency. Attaching AS1411 to gold nanospheres (AS1411-GNSs) increases its accumulation in cancer cells and enhances its antitumor efficacy by binding to cellular nucleolin. Nucleolin is associated with ribosomal DNA (rDNA) and is absolutely required for rRNA synthesis. It binds with nanomolar affinities the G-quadruplex rDNA sequences to increase the rate of RNA polymerase I (POL1) transcription. We developed a new complex of AS1411 conjugated to Gold nanospheres (GACGs). This complex was more stable and effective than AS1411 in treated tumor cell lines. GACGs decrease nucleolin expression affecting tumor cell proliferation and POLI targeting genes transcription such as 5’ETS and 18s. Thus, GACGs targeting Nucleolin/rDNA complexes inhibit POLI and represents a novel, nucleolar targeting approach to selectively disrupt proliferation in cancer cells and induce cell death.