Carborane bearing pullulan nanogel-boron oxide nanoparticle hybrid for boron neutron capture therapy

Riku Kawasaki; Hidetoshi Hirano; Keita Yamana; Hinata Isozaki; Shogo Kawamura; Yu Sanada; Kaori Bando; Anri Tabata; Kouhei Yoshikawa; Hideki Azuma; Takushi Takata; Hiroki Tanaka; Yoshinori Sakurai; Minoru Suzuki; Naoki Tarutani; Kiyofumi Katagiri; Shin-Ichi Sawada; Yoshihiro Sasaki; Kazunari Akiyoshi; Takeshi Nagasaki; Atsushi Ikeda

doi:10.1016/j.nano.2023.102659

Carborane bearing pullulan nanogel-boron oxide nanoparticle hybrid for boron neutron capture therapy

Nanomedicine. 2023 Apr:49:102659. doi: 10.1016/j.nano.2023.102659. Epub 2023 Feb 21.

Authors

Riku Kawasaki¹, Hidetoshi Hirano², Keita Yamana², Hinata Isozaki², Shogo Kawamura², Yu Sanada³, Kaori Bando⁴, Anri Tabata⁴, Kouhei Yoshikawa⁴, Hideki Azuma⁴, Takushi Takata³, Hiroki Tanaka³, Yoshinori Sakurai³, Minoru Suzuki³, Naoki Tarutani², Kiyofumi Katagiri², Shin-Ichi Sawada⁵, Yoshihiro Sasaki⁵, Kazunari Akiyoshi⁵, Takeshi Nagasaki⁴, Atsushi Ikeda⁶

Affiliations

¹ Program of Applied Chemistry, Graduate School of Advanced Science and Engineering, Hiroshima University, 1-4-1 Kagamiyama, Higashi, Hiroshima City 739-8527, Japan. Electronic address: riku0528@hiroshima-u.ac.jp.
² Program of Applied Chemistry, Graduate School of Advanced Science and Engineering, Hiroshima University, 1-4-1 Kagamiyama, Higashi, Hiroshima City 739-8527, Japan.
³ Institute for Integrated Radiation and Nuclear Science, Kyoto University, Asashiro-Nishi, Kumatori-cho, Sennan-gun, Osaka 590-0494, Japan.
⁴ Department of Applied Chemistry and Bioengineering, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka City 558-8585, Japan.
⁵ Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Kyoto-Daigaku Katsura, Nishikyo-ku, Kyoto City 615-8510, Japan.
⁶ Program of Applied Chemistry, Graduate School of Advanced Science and Engineering, Hiroshima University, 1-4-1 Kagamiyama, Higashi, Hiroshima City 739-8527, Japan. Electronic address: aikeda@hiroshima-u.ac.jp.

PMID: 36822335
DOI: 10.1016/j.nano.2023.102659

Abstract

Boron neutron capture therapy shows is a promising approach to cancer therapy, but the delivery of effective boron agents is challenging. To address the requirements for efficient boron delivery, we used a hybrid nanoparticle comprising a carborane = bearing pullulan nanogel and hydrophobized boron oxide nanoparticle (HBNGs) enabling the preparation of highly concentrated boron agents for efficient delivery. The HBNGs showed better anti-cancer effects on Colon26 cells than a clinically boron agent, L-BPA/fructose complex, by enhancing the accumulation and retention amount of the boron agent within cells in vitro. The accumulation of HBNGs in tumors, due to the enhanced permeation and retention effect, enabled the delivery of boron agents with high tumor selectivity, meeting clinical demands. Intravenous injection of boron neutron capture therapy (BNCT) using HBNGs decreased tumor volume without significant body weight loss, and no regrowth of tumor was observed three months after complete regression. The therapeutic efficacy of HBNGs was better than that of L-BPA/fructose complex. BNCT with HBNGs is a promising approach to cancer therapeutics.

Keywords: Boron neutron capture therapy; Drug delivery system; Hybrid nanoparticle; Nanogel.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Boron
Boron Compounds
Boron Neutron Capture Therapy*
Fructose
Humans
Nanogels
Neoplasms* / drug therapy
Neoplasms* / radiotherapy

Substances

boron oxide
pullulan
polyethylene glycol polyethyleneimine nanogel
Nanogels
Boron
Boron Compounds
Fructose