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局部核反应打破了装载免疫佐剂的硼药物胶囊,用于癌症免疫治疗。

Localized nuclear reaction breaks boron drug capsules loaded with immune adjuvants for cancer immunotherapy.

机构信息

Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.

The Centre of Nanoscale Science and Technology and Key Laboratory of Functional Polymer Materials, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin, 300071, China.

出版信息

Nat Commun. 2023 Apr 5;14(1):1884. doi: 10.1038/s41467-023-37253-x.

Abstract

Boron neutron capture therapy (BNCT) was clinically approved in 2020 and exhibits remarkable tumour rejection in preclinical and clinical studies. It is binary radiotherapy that may selectively deposit two deadly high-energy particles (He and Li) within a cancer cell. As a radiotherapy induced by localized nuclear reaction, few studies have reported its abscopal anti-tumour effect, which has limited its further clinical applications. Here, we engineer a neutron-activated boron capsule that synergizes BNCT and controlled immune adjuvants release to provoke a potent anti-tumour immune response. This study demonstrates that boron neutron capture nuclear reaction forms considerable defects in boron capsule that augments the drug release. The following single-cell sequencing unveils the fact and mechanism that BNCT heats anti-tumour immunity. In female mice tumour models, BNCT and the controlled drug release triggered by localized nuclear reaction causes nearly complete regression of both primary and distant tumour grafts.

摘要

硼中子俘获治疗(BNCT)于 2020 年获得临床批准,在临床前和临床研究中表现出显著的肿瘤排斥反应。它是一种二元放疗,可以在癌细胞内选择性地沉积两种致命的高能粒子(氦和锂)。作为一种由局部核反应诱导的放疗,很少有研究报道其远隔抗肿瘤效应,这限制了其进一步的临床应用。在这里,我们设计了一种经中子激活的硼胶囊,它协同 BNCT 和控制的免疫佐剂释放,引发强烈的抗肿瘤免疫反应。本研究表明,硼中子俘获核反应在硼胶囊中形成了大量的缺陷,从而增强了药物的释放。随后的单细胞测序揭示了 BNCT 加热抗肿瘤免疫的事实和机制。在雌性小鼠肿瘤模型中,BNCT 和局部核反应触发的药物控释导致原发性和远处肿瘤移植物几乎完全消退。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/935e/10076324/2ba53eaefdfa/41467_2023_37253_Fig1_HTML.jpg

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