Silicon-based nanoprobes cross the blood–brain barrier for photothermal therapy of glioblastoma
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Houyu Wang(
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Traditional photothermal agents of indocyanine green (ICG) have poor stability, short circulation time, and poor brain permeability due to the blood–brain barrier (BBB), greatly impairing their therapeutic efficacy in glioblastoma (GBM). Herein, we develop a novel kind of SiNPs-based nanoprobes to bypass the BBB for photothermal therapy of GBM. Typically, the SiNPs-based nanoprobes are composed of the particle itself, the BBB-targeting ligand of glucosamine (G), and the therapeutic agent of ICG. We demonstrate that the as-synthesized nanoprobes could cross the BBB through glucose transporter-1 (GLUT1)-mediated transcytosis, followed by accumulation at GBM tissues in mice. Compared with free ICG, G-ICG-SiNPs show stronger stability (for example, the fluorescence intensity of G-ICG-SiNPs loaded with the same dose of ICG decays by 34.6% after 25 days of storage, while the fluorescence intensity of ICG decays by 99.5% under the same conditions). Furthermore, the blood circulation time of G-ICG-SiNPs increases by about 17.3-fold compared with their ICG counterparts. After injection of the therapeutic agents into the GBM-bearing mice, GBM-surface temperature rises to 45.3 °C in G-ICG-SiNPs group after 5-min 808 nm irradiation but climbs only to 36.1 °C in equivalent ICG group under the identical conditions, indicating the superior photothermal effects of G-ICG-SiNPsin vivo.
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Silicon-based nanoprobes cross the blood–brain barrier for photothermal therapy of glioblastoma
), Houyu Wang(
)
Abstract
Traditional photothermal agents of indocyanine green (ICG) have poor stability, short circulation time, and poor brain permeability due to the blood–brain barrier (BBB), greatly impairing their therapeutic efficacy in glioblastoma (GBM). Herein, we develop a novel kind of SiNPs-based nanoprobes to bypass the BBB for photothermal therapy of GBM. Typically, the SiNPs-based nanoprobes are composed of the particle itself, the BBB-targeting ligand of glucosamine (G), and the therapeutic agent of ICG. We demonstrate that the as-synthesized nanoprobes could cross the BBB through glucose transporter-1 (GLUT1)-mediated transcytosis, followed by accumulation at GBM tissues in mice. Compared with free ICG, G-ICG-SiNPs show stronger stability (for example, the fluorescence intensity of G-ICG-SiNPs loaded with the same dose of ICG decays by 34.6% after 25 days of storage, while the fluorescence intensity of ICG decays by 99.5% under the same conditions). Furthermore, the blood circulation time of G-ICG-SiNPs increases by about 17.3-fold compared with their ICG counterparts. After injection of the therapeutic agents into the GBM-bearing mice, GBM-surface temperature rises to 45.3 °C in G-ICG-SiNPs group after 5-min 808 nm irradiation but climbs only to 36.1 °C in equivalent ICG group under the identical conditions, indicating the superior photothermal effects of G-ICG-SiNPsin vivo.
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Acknowledgements
The authors acknowledge financial support from the National Natural Science Foundation of China (Nos. 21825402 and 22074101), the Natural Science Foundation of Jiangsu Province of China (No. BK20191417), the China Postdoctoral Science Foundation (No. 2021M692347), and the Program for Jiangsu Specially-Appointed Professors to the Prof. Yao He, a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), the 111 Project, as well as the Collaborative Innovation Center of Suzhou Nano Science and Technology (NANO-CIC).
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