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Exosome-Coated 10B Carbon Dots for Precise Boron Neutron Capture Therapy in a Mouse Model of Glioma In Situ

Journal 2021 · IF 18.808 · 31(24): 2100969 · 发表于 2021 年 4 月 8 日
作者: Juan Li,Jianglong Kong,Sihan Ma,Jiacheng Li,Meiru Mao,Kui Chen,Ziteng Chen,Jiaxin Zhang,Yanan Chang,Hui Yuan,Tong Liu,Zizhu Zhang,Gengmei Xing
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摘要

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 10 B in vitro and in vivo. Encapsulation of BCDs using exosomes (Exos) from macrophages yields BCD–Exos of ≈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 10 B 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.

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