Block copolymer-boron cluster conjugate for effective boron neutron capture therapy of solid tumors

Peng Mi; Hironobu Yanagie; Novriana Dewi; Hung-Chi Yen; Xueying Liu; Minoru Suzuki; Yoshinori Sakurai; Koji Ono; Hiroyuki Takahashi; Horacio Cabral; Kazunori Kataoka; Nobuhiro Nishiyama

doi:10.1016/j.jconrel.2017.03.036

Block copolymer-boron cluster conjugate for effective boron neutron capture therapy of solid tumors

J Control Release. 2017 May 28:254:1-9. doi: 10.1016/j.jconrel.2017.03.036. Epub 2017 Mar 21.

Authors

Affiliations

¹ 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.
² Department of Nuclear Engineering and Management, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
³ Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
⁴ Innovation Center of Nanomedicine (iCONM), 3-25-14 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.
⁵ Radiation Oncology Research Laboratory, Research Reactor Institute, Kyoto University, Osaka 2 Asahiro nishi, Kumatori, Sennan, Osaka 590-0494, Japan.
⁶ 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.
⁷ 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.
⁸ 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.

PMID: 28336377
DOI: 10.1016/j.jconrel.2017.03.036

Abstract

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 of ¹⁰B-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.

Keywords: Boron neutron capture therapy; Drug delivery system; Polymer-drug conjugate; Sodium borocapate; Tumor penetration.

MeSH terms

Animals
Borohydrides / chemistry*
Boron Neutron Capture Therapy / methods*
Cell Line, Tumor
Cell Survival
Chemistry, Pharmaceutical
Drug Delivery Systems / methods*
Drug Liberation
Female
Humans
Mice, Inbred BALB C
Mice, Nude
Neoplasms / radiotherapy*
Permeability
Polyethylene Glycols / chemistry*
Polyglutamic Acid / chemistry*
Sulfhydryl Compounds / chemistry*

Substances

Borohydrides
Sulfhydryl Compounds
poly(ethylene glycol)-block-poly(glutamic acid)
mercaptoundecahydrododecaborate
Polyglutamic Acid
Polyethylene Glycols