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

Abstract

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 10B 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 10B 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 10B 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.

Overcoming the blood–brain barrier for the therapy of malignant brain tumor: current status and prospects of drug delivery approaches

“…In another study by Qiao et al, the authors developed the CDs modified with d-glucose and l-aspartic for targeting brain tumor cells (C6 cells) [336]. Recently, Li et al prepared exosome-coated 10 B-CDs for BNCT of brain tumors, which was demonstrated on a glioma mice model [337]. The excellent accumulation of these CDs in the brain glioma in vivo allowed an effective BNCT, achieving a prolonged survival rate of mice compared to control samples (a survival ratio of 100% for 30 days in case of BNCT and a survival ratio of 0% after 15 days of experiments in case of control group, i.e.…”

“…The excellent accumulation of these CDs in the brain glioma in vivo allowed an effective BNCT, achieving a prolonged survival rate of mice compared to control samples (a survival ratio of 100% for 30 days in case of BNCT and a survival ratio of 0% after 15 days of experiments in case of control group, i.e. mice without therapy) [337].…”

Recent progress of carbon dots in targeted bioimaging and cancer therapy

“…Except the above strategy to achieve cancer therapy, there are still other advanced nanotechnology to be developed with CDs for diverse cancer. For example, boron neutron capture therapy (BNCT) was a noninvasive radiation therapeutic modality for cancer therapy and Li et al designed one kind of novel boron-containing carbon dots (BCDs) for the BNCT by tracking 10B in vitro and in vivo 234 . With the encapsulation of BCDs by exosomes (Exos), researchers designed the BCD-Exos which could internalize and distribute around the nuclei of U-87-MG glioma cells (Figure 20 A-B).…”

“…(E) Gross images of mice brains and microscopic images of H&E-stained tumor sections in each group. Adapted with permission from 234 , copyright 2021 Wiley-VCH GmbH.…”

Modernistic and Emerging Developments of Nanotechnology in Glioblastoma-Targeted Theranostic Applications

“…Li et al prepared boron CDs using boron phenylalanine (BPA) and glucose as precursors through hydrothermal heating and coating by exosomes to explore the activity of boron neutron capture therapy (BNCT) against glioma in mice. More importantly, these nanomaterials have shown a more excellent permeability across the BBB than the CDs alone (staying only up to 15 min), and then they shed from the brain [37]. Furthermore, their fluorescence imaging properties are adequate for precisely identifying glioma, which qualifies these materials as "promising theranostics".…”