Targeting glioma stem cells enhances anti-tumor effect of boron neutron capture therapy

// Ting Sun 1 , Yanyan Li 1 , Yulun Huang 1 , Zizhu Zhang 2 , Weilian Yang 1 , Ziwei Du 1 , Youxin Zhou 1 1 Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China 2 Beijing Capture Tech Co., Ltd, Beijing, China Correspondence to: Youxin Zhou, email: brain_lab@suda.edu.cn Keywords: boron neutron capture therapy, glioma stem cells, target, CD133, bioconjugate Received: January 31, 2016      Accepted: April 26, 2016      Published: May 13, 2016 ABSTRACT The uptake of (10) boron by tumor cells plays an important role for cell damage in boron neutron capture therapy (BNCT). CD133 is frequently expressed in the membrane of glioma stem cells (GSCs), resistant to radiotherapy and chemotherapy, and represents a potential therapeutic target. To increase (10) boron uptake in GSCs, we created a polyamido amine dendrimer, conjugated CD133 monoclonal antibodies, encapsulating mercaptoundecahydrododecaborate (BSH) in void spaces, and monitored the uptake of the bioconjugate nanoparticles by GSCs in vitro and in vivo . Fluorescence microscopy showed the specific uptake of the bioconjugate nanoparticles by CD133-positive GSCs. Treatment with the biconjugate nanoparticles resulted in a significant lethal effect after neutron radiation due to efficient and CD133-independent cellular targeting and uptake in CD133-expressing GSCs. A significantly longer survival occurred in combination with the biconjugate nanoparticles and BSH compared with BSH alone in human intracranial GBM models employing CD133-positive GSCs xenografts. Our data demonstrated that this bioconjugate nanoparticle targets human CD133-positive GSCs and is a potential boron agent in BNCT.