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

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.

Automated summary

Novel boron-containing carbon dots (BCDs) were designed and prepared for boron neutron capture therapy (BNCT), encapsulated in exosomes (Exos) from macrophages to form BCD-Exos, achieving excellent therapeutic effects on brain glioma in mice models with 100% survival rate. Adjusted biodistribution of boron, enhanced T/N ratios, and precise match between boron and neutron exposure at the tumor site in vivo with fluorescence imaging of BCD-Exos contributed to the success of the treatment.