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
We report that atomically thin two-dimensional silicon quantum sheets(2D Si QSs),prepared by a scalable approach coupling chemical delithiation and cryo-assisted exfoliation,can serve as a highperformance brain photon...We report that atomically thin two-dimensional silicon quantum sheets(2D Si QSs),prepared by a scalable approach coupling chemical delithiation and cryo-assisted exfoliation,can serve as a highperformance brain photonic nanoagent for orthotopic glioma theranostics.With the lateral size of approximately 14.0 nm and thickness of about 1.6 nm,tiny Si QSs possess high mass extinction coefficient of 27.5 Lg^(-1)cm^(-1)and photothermal conversion efficiency of 47.2%at 808 nm,respectively,concurrently contributing to the best photothermal performance among the reported 2 D mono-elemental materials(Xenes).More importantly,Si QSs with low toxicity maintain the trade-off between stability and degradability,paving the way for practical clinical translation in consideration of both storage and action of nanoagents.In vitro Transwell filter experiment reveals that Si QSs could effectively go across the b End.3 cells monolayer.Upon the intravenous injection of Si QSs,orthotopic brain tumors are effectively inhibited under the precise guidance of photoacoustic imaging,and the survival lifetime of brain tumor-bearing mice is increased by two fold.Atomically thin Si QSs with strong light-harvesting capability are expected to provide an effective and robust 2D photonic nanoplatform for the management of brain diseases.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.
基金supported by the National Key Research and Development Program of China:Scientific and Technological Innovation Cooperation of Mainland and Macao(2017YFE0120000)the National Natural Science Foundation of China(31800834,81527901,81571745,91859117,81771906,81827807,81901812,and 52071120)+6 种基金the Open Foundation of Shenzhen Bay Laboratory(SZBL2019062801005)the Fundamental Research Funds for the Central Universities(JZ2020HGTB0031 and JZ2018HGPA0273)the Science and Technology Key Project of Shenzhen(JCYJ20160229200902680)the Shenzhen Key Laboratory of Ultrasound Imaging and Therapy(ZDSYS201802061806314)the Shenzhen Double Chain Grant([2018]256)the Natural Science Foundation of Guangdong Province(2014A030312006)the China Postdoctoral Science Foundation(2019 M653129)。
文摘We report that atomically thin two-dimensional silicon quantum sheets(2D Si QSs),prepared by a scalable approach coupling chemical delithiation and cryo-assisted exfoliation,can serve as a highperformance brain photonic nanoagent for orthotopic glioma theranostics.With the lateral size of approximately 14.0 nm and thickness of about 1.6 nm,tiny Si QSs possess high mass extinction coefficient of 27.5 Lg^(-1)cm^(-1)and photothermal conversion efficiency of 47.2%at 808 nm,respectively,concurrently contributing to the best photothermal performance among the reported 2 D mono-elemental materials(Xenes).More importantly,Si QSs with low toxicity maintain the trade-off between stability and degradability,paving the way for practical clinical translation in consideration of both storage and action of nanoagents.In vitro Transwell filter experiment reveals that Si QSs could effectively go across the b End.3 cells monolayer.Upon the intravenous injection of Si QSs,orthotopic brain tumors are effectively inhibited under the precise guidance of photoacoustic imaging,and the survival lifetime of brain tumor-bearing mice is increased by two fold.Atomically thin Si QSs with strong light-harvesting capability are expected to provide an effective and robust 2D photonic nanoplatform for the management of brain diseases.
