Block copolymer-boron cluster conjugate for effective boron neutron capture therapy of solid tumors.
Boron neutron capture therapy is a promising tumor treatment method, though its wide application has been limited due to the poor tumor selectivity and intracellular delivery of10B-compounds. Here, block copolymer-boron cluster conjugate based on the clinically used sodium borocaptate (BSH) and poly(ethylene glycol)-b-poly(glutamic acid) copolymer have been developed for effectively penetrating tumor tissues and homogeneously delivering the boron clusters into cancer cells towards safe and efficient boron neutron capture therapy. The PEGylated block copolymer-boron cluster (BSH) conjugate has demonstrated significant higher cellular uptake and tumor accumulation when compared to the non-PEGylated formulations and BSH. Moreover, the enhanced delivery to tumors of the conjugates, as well as their superior intratumoral penetration, which facilitated reaching the intracellular space of most cells in tumors, allowed the effective ablation of tumors after neutron irradiation.
Department of Radiology, Center for Medical Imaging, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, PR China. Electronic address: mi@scu.edu.cn.
Peng
P
Mi
Department of Nuclear Engineering and Management, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Hironobu
H
Yanagie
Department of Nuclear Engineering and Management, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Novriana
N
Dewi
Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Hung-Chi
HC
Yen
Innovation Center of Nanomedicine (iCONM), 3-25-14 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.
Xueying
X
Liu
Radiation Oncology Research Laboratory, Research Reactor Institute, Kyoto University, Osaka 2 Asahiro nishi, Kumatori, Sennan, Osaka 590-0494, Japan.
Minoru
M
Suzuki
Radiation Oncology Research Laboratory, Research Reactor Institute, Kyoto University, Osaka 2 Asahiro nishi, Kumatori, Sennan, Osaka 590-0494, Japan.
Yoshinori
Y
Sakurai
Radiation Oncology Research Laboratory, Research Reactor Institute, Kyoto University, Osaka 2 Asahiro nishi, Kumatori, Sennan, Osaka 590-0494, Japan.
Koji
K
Ono
Department of Nuclear Engineering and Management, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Hiroyuki
H
Takahashi
Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan. Electronic address: horacio@bmw.t.u-tokyo.ac.jp.
Horacio
H
Cabral
Innovation Center of Nanomedicine (iCONM), 3-25-14 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan; Policy Alternatives Research Institute, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan. Electronic address: kataoka@bmw.t.u-tokyo.ac.jp.
Kazunori
K
Kataoka
Innovation Center of Nanomedicine (iCONM), 3-25-14 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan; Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, R1-11, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan. Electronic address: nishiyama.n.ad@m.titech.ac.jp.
Nobuhiro
N
Nishiyama
D000818:Animals; D001894:Borohydrides / Q000737:chemistry*; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D045744:Cell Line, Tumor; D002470:Cell Survival; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D005260:Female; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000532:radiotherapy*; D010539:Permeability; D011092:Polyethylene Glycols / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry*
D001894:Borohydrides; D013438:Sulfhydryl Compounds; C575477:poly(ethylene glycol)-block-poly(glutamic acid); C014651:mercaptoundecahydrododecaborate; D011099:Polyglutamic Acid; D011092:Polyethylene Glycols
Boron neutron capture therapy; Drug delivery system; Polymer-drug conjugate; Sodium borocapate; Tumor penetration