Eradication of Glioblastoma Multiforme stem-cells with Immunotargeted-molecular-robotic-NANOSURGERY (ITMRN)

Abstract

GBM stem cells are resistant to conventional treatment forming recurrent-tumors via angiogenesis.Thus,they are considered primary targets for novel therapeutic strategies for GBM. We obtain relapsed chemo-radioresistant GBM stem cells overexpressing CD133 from which we develop a GBM model that we treat with immunotargeted pegylated silver nanobots(PEG-AgNPs) which are covalently conjugated to anti-CD133 MAbs for targeting Brain-Cancer-Stem-Cells(BCSCs) after receptor-mediated-endocytosis.Then,we treat them with radiofrequency-dielectric-heating(RFDH) as a novel postsurgical-adjuvant-treatment. Post-treatment,the silver nanobots AgNPs release Ag+ ions which disrupt mitochondrial-respiratory-chain(MRC) blocking ATP-synthesis by production of ROS which damage the DNA of CSCs leading to cell-cycle arrest at G2/M phase and type-1 PCD of stage-D2 or apoptosis.The capacitive nonionizing radiofrequency-dielectric-heating of 13.56MHz exerts hyperthermic cytotoxicity increasing the intracellular-Temperature of BCSCs up to 50 degrees Celcius leading to the necrosis of Brain-Cancer-Stem-Cells(BCSCs). This immunotargeted molecular robotic nanosurgical approach may be used as an adjuvant treatment against GBM which is resistant to conventional chemo/radiation therapy by eradicating its cancer-stem-cells.