Exosome-Coated 10B Carbon Dots for Precise Boron Neutron Capture Therapy in a Mouse Model of Glioma In Situ
Exosome-Coated 10B Carbon Dots for Precise Boron Neutron Capture Therapy in a Mouse Model of Glioma In Situ
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DOI：
10.1002/adfm.202100969
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发表时间：
2021-04-08
影响因子：
19
通讯作者：
Xing, Gengmei
中科院分区：
文献类型：
--
作者：
Li, Juan;Kong, Jianglong;Xing, Gengmei
设计并制备了用于硼中子俘获治疗(BNCT)的新型含硼碳点(BCDS)，该碳点具有优异的水溶性和良好的光学性能，可在体内外跟踪B-10。用巨噬细胞的外切体(Exos)包裹BCDS，可产生约100 nm的BCD-Exos。荧光成像显示，BCD-Exos内化并分布在U-87-MG胶质瘤细胞的细胞核周围。BCD-Exos在U-87-MG脑胶质瘤原位移植瘤模型小鼠体内给药后4h即可通过血脑屏障，并在肿瘤组织内显著蓄积。电感耦合等离子体质谱检测到肿瘤组织中的B-10含量为107.07+/-1.58ppm，其T/N值从苯丙氨酸硼的2.03+/-0.08提高到BCD-Exos的5.28+/-0.29。在BNCT中，当剂量为500 mg kg(-110)B时，中子辐射剂量为8.40+/-0.12Gy.BCD-Exos治疗的小鼠脑胶质瘤模型有明显的BNCT效应，实验结束时存活率为100%。使用BCD-Exos的BNCT治疗脑胶质瘤的良好疗效是通过调整B在癌细胞中的生物分布，提高T/N比，以及BCD-Exos荧光成像在体内肿瘤部位硼与中子照射的精确匹配而实现的。
Novel boron-containing carbon dots (BCDs) are designed and prepared for boron neutron capture therapy (BNCT) with superior water solubility and excellent optical property for tracking B-10 in vitro and in vivo. Encapsulation of BCDs using exosomes (Exos) from macrophages yields BCD-Exos of approximate to 100 nm. Fluorescent imaging shows that the BCD-Exos are internalized and distributed around the nuclei of U-87-MG glioma cells. BCD-Exos are also verified to cross the blood-brain barrier and significant accumulation in tumor tissue of the orthotopic U-87-MG glioma tumor-bearing mice model 4 h after administration. Using inductively coupled plasma mass spectrometry (ICP-MS), it is detected that B-10 in tumor tissue is 107.07 +/- 1.58 ppm, and T/N ratios are enhanced from 2.03 +/- 0.08 of boron phenylalanine (BPA) to 5.28 +/- 0.29 of the BCD-Exos. In BNCT, the neutron radiation dose is 8.40 +/- 0.12 Gy when a 500 mg kg(-1 10)B dosage is given. Finally, there is a prominent BNCT effect of the BCD-Exos-treated brain glioma in the mice model, and the survival ratio is 100% at the end of the experiment. The excellent curative effect of BNCT using BCD-Exos to brain glioma is achieved through adjusted biodistribution of boron in the cancer cell, enhanced T/N ratios, and the precise match between boron and neutron exposure in the site of the tumor in vivo with fluorescence imaging of BCD-Exos.