Focused ultrasound(FUS)-induced blood–brain barrier(BBB) opening is crucial for enhancing glioblastoma(GBM) therapies. However, an in vivo imaging approach with a high spatial–temporal resolution to monitor the BBB ...Focused ultrasound(FUS)-induced blood–brain barrier(BBB) opening is crucial for enhancing glioblastoma(GBM) therapies. However, an in vivo imaging approach with a high spatial–temporal resolution to monitor the BBB opening process in situ and synchronously is still lacking. Herein, we report the use of indocyanine green(ICG)-dopped microbubbles(MBs-ICG) for visualizing the FUS-induced BBB opening and enhancing the photothermal therapy(PTT) against GBM. The MBs-ICG show bright fluorescence in the second near-infrared window(NIR-II), ultrasound contrast, and ultrasound-induced size transformation properties. By virtue of complementary contrast properties, MBs-ICG can be successfully applied for cerebral vascular imaging with NIR-II fluorescence resolution of ~168.9 lm and ultrasound penetration depth of ~7 mm. We further demonstrate that MBs-ICG can be combined with FUS for in situ and synchronous visualization of the BBB opening with a NIR-II fluorescence signal-tobackground ratio of 6.2 ± 1.2. Finally, our data show that the MBs-ICG transform into lipid-ICG nanoparticles under FUS irradiation, which then rapidly penetrate the tumor tissues within 10 min and enhance PTT in orthotopic GBM-bearing mice. The multifunctional MBs-ICG approach provides a novel paradigm for monitoring BBB opening and enhancing GBM therapy.展开更多
基金supported by the National Natural Science Foundation of China (92159304, 82171958, 81901812, 81971638, 91859117, 82027803, and 81927807)CAS Key Laboratory of Health Informatics (2011DP173015)+4 种基金the Science and Technology Key Project of Shenzhen(JCYJ20190812163614809, JCYJ20200109114612308, JCYJ2021032 4120011030, JCYJ20190809105207439, JCYJ20220531091408019, and JCYJ20200109114825064)Guangdong Basic and Applied Basic Research Fund (2020A1515110011, 2020A1515010395, and 2022A1515010384)Key Laboratory for Magnetic Resonance and Multimodality Imaging of Guangdong Province (2020B1212060051)the Key Technology and Equipment R&D Program of Major Science and Technology Infrastructure of Shenzhen (202100102, 202100104)Discipline Construction Project of Guangdong Medical University (4SG21017G)
文摘Focused ultrasound(FUS)-induced blood–brain barrier(BBB) opening is crucial for enhancing glioblastoma(GBM) therapies. However, an in vivo imaging approach with a high spatial–temporal resolution to monitor the BBB opening process in situ and synchronously is still lacking. Herein, we report the use of indocyanine green(ICG)-dopped microbubbles(MBs-ICG) for visualizing the FUS-induced BBB opening and enhancing the photothermal therapy(PTT) against GBM. The MBs-ICG show bright fluorescence in the second near-infrared window(NIR-II), ultrasound contrast, and ultrasound-induced size transformation properties. By virtue of complementary contrast properties, MBs-ICG can be successfully applied for cerebral vascular imaging with NIR-II fluorescence resolution of ~168.9 lm and ultrasound penetration depth of ~7 mm. We further demonstrate that MBs-ICG can be combined with FUS for in situ and synchronous visualization of the BBB opening with a NIR-II fluorescence signal-tobackground ratio of 6.2 ± 1.2. Finally, our data show that the MBs-ICG transform into lipid-ICG nanoparticles under FUS irradiation, which then rapidly penetrate the tumor tissues within 10 min and enhance PTT in orthotopic GBM-bearing mice. The multifunctional MBs-ICG approach provides a novel paradigm for monitoring BBB opening and enhancing GBM therapy.
