Recently, Zhibo Liu group from the College of Chemistry and Molecular Engineering,Peking University reported boronsome, a carboranyl-phosphatidylcholine based liposome, for combinational BNCT (boron neutron capture therapy) and chemotherapy. The study was published in Nature Communications on April 19, 2022 (https://doi.org/10.1038/s41467-022-29780-w), with the title “Boron encapsulated in a liposome can be used for combinational neutron capture therapy”.
Boron-10 capture thermal neutrons, yield α particles that deposit high energy over a very brief pathway (5–9 μm, approximately the diameter of a single cell), then damage the tumor cells. This unique type of radiation therapy that enables the targeting of cancer with cellular-level precision is known as boron neutron capture therapy (BNCT). Based on the combination of neutron irradiation and the administration of 10B compounds, BNCT could provide accurate and excellent control over locally invasive malignant as a binary treatment modality. However, to perform successful BNCT, boron delivery agents with high tumor accumulation, high in vivo stability, and low biochemical toxicity are required. Boronophenylalanine (BPA) has been the dominating boron delivery agent in clinics for decades. But the clinical applications of BPA have been hampered by low boron content, poor tumor selectivity, and a lack of imaging techniques to monitor boron concentration and biodistribution in real-time.
Fig. 1 Schematic diagram of the structure and function of boronsome for BNCT.
In recent years, Zhibo Liu group has studied the unique chemical and radiation biological effects of BNCT and developed a variety of theranostic boron delivery systems, including boron-derived tyrosine (fluoroboronotyrosine, FBY), carborane micelles, and boron nitride nanoparticles, received Fairchild Award from the international society for neutron capture therapy.
In this work, the carboranyl group with high stability and hydrophobicity is covalently conjugated to the hydrophobic tail of phospholipids to form boronated phospholipids, assembled to form a new class of boron-containing liposomes, denoted as boronsomes. Boronsome has good biocompatibility, high-specific tumor accumulation, long retention with a clear irradiation background, and could deliver more boron into tumors than BPA. By incorporating radiolabeled boronsome, PET imaging is adopted as a non-invasive technique to monitor tissue-specifically boron concentration and biodistribution in real-time precisely, assisting in the determination of irradiation radius and time point. In addition, by encapsulating chemotherapy drugs (such as PARP1 inhibitor) within boronsome, high-LET particles emitting and drug release occur almost simultaneously during neutron beam irradiation, enabling cell damage synergistically, then improving the efficacy of BNCT. In sum, boronsome suppresses tumor growth as an effective boron delivery platform, with safe, traceable tumor-targeted boron enrichment and concurrent chemoradiotherapy, which has high clinical potential.
Dr. Jiyuan Li and Qi Sun are the co-first authors of this paper. Prof. Zhibo Liu is the corresponding author. Other collaborators include Tong Liu and Zizhu Zhang from Beijing Capture Tech Co., Ltd. This research was funded by the National Natural Science Foundation of China, the Ministry of Science and Technology of the People's Republic of China, the Beijing Municipal Natural Science Foundation, the Special Foundation of Beijing Municipal Education Commission, and Peking University Ge Li and Ning Zhao Life Science Research Fund for Young Scientists.
Original link: https://www.nature.com/articles/s41467-022-29780-w#Fig1
