title: Targeting glioma stem cells enhances anti-tumor effect of boron neutron capture therapy.
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.
authors.affiliation: Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Sun
authors.affiliation: Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Yulun
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Beijing Capture Tech Co., Ltd, Beijing, China.
authors.forename: Zizhu
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Weilian
authors.initials: W
authors.lastname: Yang
authors.affiliation: Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Du
authors.affiliation: Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Youxin
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000071916:AC133 Antigen / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000074322:Antineoplastic Agents, Immunological / Q000008:administration & dosage / Q000627:therapeutic use*; D001894:Borohydrides / Q000008:administration & dosage; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism / Q000528:radiation effects*; D050091:Dendrimers / Q000737:chemistry; D005910:Glioma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D058726:Nanoconjugates / Q000737:chemistry; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000528:radiation effects*; D013438:Sulfhydryl Compounds / Q000008:administration & dosage; D023041:Xenograft Model Antitumor Assays
chemical_list: D000071916:AC133 Antigen; D000074322:Antineoplastic Agents, Immunological; D001894:Borohydrides; D050091:Dendrimers; D058726:Nanoconjugates; C104700:PAMAM Starburst; C000606023:PROM1 protein, human; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate
keywords: CD133; bioconjugate; boron neutron capture therapy; glioma stem cells; target