PEGylated liposome encapsulating nido-carborane showed significant tumor suppression in boron neutron capture therapy (BNCT)

碳硼烷 脂质体 放射化学 中子俘获 化学 中子温度 生物物理学 核化学 材料科学 中子 生物化学 有机化学 量子力学 生物 物理
作者
Woonghee Lee,Swarbhanu Sarkar,Hyung Joon Ahn,Jung Young Kim,Yong Jin Lee,Yongmin Chang,Jeongsoo Yoo
出处
期刊:Biochemical and Biophysical Research Communications [Elsevier]
卷期号:522 (3): 669-675 被引量:32
标识
DOI:10.1016/j.bbrc.2019.11.144
摘要

Boron neutron capture therapy (BNCT) is a binary radiotherapy based on nuclear reactions that occur when boron-10 is irradiated with neutrons, which result in the ejection of high-energy alpha particles. Successful BNCT requires the efficient delivery of a boron-containing compound to effect high concentrations in tumor cells while minimizing uptake in normal tissues. In this study, PEGylated liposomes were employed as boron carriers to maximize delivery to tumors and minimize uptake in the reticuloendothelial system (RES). The water-soluble potassium salt of nido-7,8-carborane, nido-carborane, was chosen as the boron source due to its high boron content per molecule. Nido-carborane was encapsulated in the aqueous cores of PEGylated liposomes by hydrating thin lipid films. Repeated freezing and thawing increased nido-carborane loading by up to 47.5 ± 3.1%. The average hydrodynamic diameter of the prepared boronated liposomes was determined to be 114.5 ± 28 nm through dynamic light scattering (DLS) measurement. Globular liposomes approximately 100 nm in diameter were clearly visible in transmission electron microscope (TEM) images. The viability of tumor cells following BNCT with 70 μM nido-carborane was reduced to 17.1% compared to irradiated control cells, which did not contain boronated liposomes. Confocal microscopy revealed that fluorescently labeled liposomes injected into the tail veins of mice were deeply and evenly distributed in tumor tissues and localized in the cytoplasm of tumor cells. When mice were properly shielded with a 12 mm-thick polyethylene board during in-vivo irradiation at a thermal neutron flux of 1.94 × 104/cm2·sec, almost complete tumor suppression was achieved in tumor models injected with boronated liposomes (21.0 mg 10B/kg). Two BNCT cycles spaced 10 days apart further enhanced the therapeutic anti-tumor effect, even when the dose was lowered to 10.5 mg 10B/kg. No notable weight loss was observed in the tumor models during the BNCT study.
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