TMIC-01TUMOR TARGETED QUANTUM DOTS TO IDENTIFY GLIOMA INITIATING CELLS AND EXOSOMES

Abstract

TUMOR MICROENVIRONMENT TMIC-01. TUMOR TARGETED QUANTUM DOTS TO IDENTIFY GLIOMA INITIATING CELLS AND EXOSOMES Achutha Madhankumar, Oliver Mrowczynski, Suhag Patel, Elias Rizk, Cody Weston, Michael Glantz, Lichong Xu, Christopher Siedlecki, and James Connor; Pennsylvania State University College of Medicine, Hershey, PA, USA GBM and certain brain metastatic cancers possess invasiveness and high infiltrating potential making them harder to detect at the earlier stage of the disease progression. Identification of cancer stem cells and exosomes secreted by them in the biofluids like CSF will be an ideal way to determine the presence of residual cancer after therapy. We utilize ligand conjugated quantum dots (QD) to specifically label the cancer stem cells and exosomes to identify the presence of certain invasive markers. Human glioma initiating cells were cultured in adherent form and were exposed to interleukin-13 conjugated quantum dots (IL13QD), which binds the glioma initiating cells expressing IL13Ra2 receptor and also the exosomes secreted by the glioma stem cells. Exosomes that were isolated from glioma stem cells and patients CSF were demonstrated to express IL13Ra2 receptor. Fluorescent microscopy, electron microscopy and flow cytometry were performed on the exosomes after complexing with nano quantum dots (QD). IL13QD was demonstrated to specifically bind glioma stem cells both in the monolayer and spheroid culture. The binding affinity of the exosomes to the quantum dots were also confirmed by atomic force microscopy. The morphology and size of exosomes were confirmed by electron microscopy and dynamic light scattering method. The density plot from the flow cytometer experiments with IL13QD-exosomes complex indicates a possibility to identify the tumor associated exosomes. Our experiment infers that in ex vivo, tumor targeted quantum dots can bind with tumor initiating glioma stem cells and extracellular vesicles (exosomes) that are secreted by cancer cells. There is a future possibility to differentiate the metastatic tumor associated exosomes from the non-metastatic exosomes based on their QD binding profile Neuro-Oncology 17:v221–v225, 2015. doi:10.1093/neuonc/nov236.1 Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2015.