Boron-conjugated hyaluronan nanoparticles for Tumor Targeting in Boron Neutron Capture Therapy

Research Project

Project/Area Number	24591855
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Radiation science
Research Institution	Hiroshima International University
Principal Investigator	KASAOKA Satoshi 広島国際大学, 薬学部, 准教授 (90338690)
Project Period (FY)	2012-04-01 – 2015-03-31
Project Status	Completed (Fiscal Year 2014)
Budget Amount *help	¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000) Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000) Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords	BNCT / hyaluronic acid / nanoparticle / tumor / targeting / リポソーム / 細胞透過性ペプチド / ミセル / ヒアルロン酸
Outline of Final Research Achievements	Whave developed a novel boron delivery system for BNCT using hyaluronan conjugated with borocaptate (BSH). This BSH-bearing hyaluronan nanoparticles (B-HA-NPs) are expected to deliver boron atoms into melanoma cells by receptor　mediated endocytosis for antitumor application in BNCT.Novel BSH-bearing hyaluronan nanoparticles were obtained by the self-assembly in water. The critical micellar concentration of B-HA-NPs (diameter: 90-180 nm) was determined by the fluorescence probe technique using pyrene. B-HA-NPs had high stability in the retention of 10B during storage at 4-37 ℃. All boborocaptate-loaded formulations had no cytotoxic effects. B-HA-NPs were readily bound to melanoma cells, and were internalized by receptor-mediated endocytosis. Survival of the washed cells preincubated with B-HA-NPs was lowest compared to survival of control cells that were pre-incubated with B-PEG-liposomes, B-HA-liposomes, B-FA-conjugates and BSH solution.