Cavitation-assisted sonothrombolysis by asymmetrical nanostars for accelerated thrombolysis

Wonseok Choi; Jaehong Key; Inchan Youn; Hyojin Lee; Sungmin Han

doi:10.1016/j.jconrel.2022.09.008

Cavitation-assisted sonothrombolysis by asymmetrical nanostars for accelerated thrombolysis

Wonseok Choi, Jaehong Key, Inchan Youn, Hyojin Lee, Sungmin Han

Division of Medical Engineering

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

Abstract

Sonothrombolysis with recombinant tissue plasminogen activator (rtPA) and microbubbles has been widely studied to enhance thrombolytic potential. Here, we report different sonothrombolysis strategy in nanoparticles using microbubbles cavitation. We found that different particles in shape exhibited different reactivity toward the cavitation, leading to a distinct sonothrombolytic potential. Two different gold nanoparticles in shape were functionalized with the rtPA: rtPA-functionalized gold nanospheres (NPt) and gold nanostars (NSt). NPt could not accelerate the thrombolytic potential with a sole acoustic stimulus. Importantly, NSt enhanced the potential with acoustic stimulus and microbubble-mediated cavitation, while NPt were not reactive to cavitation. Coadministration of NSt and microbubbles resulted in a dramatic reduction of the infarcts in a photothrombotic model and recovery in the cerebral blood flow. Given the synergistic effect and in vivo feasibility of this strategy, cavitation-assisted sonothrombolysis by asymmetrical NSt might be useful for treating acute ischemic stroke.

Original language	English
Pages (from-to)	870-885
Number of pages	16
Journal	Journal of Controlled Release
Volume	350
DOIs	https://doi.org/10.1016/j.jconrel.2022.09.008
Publication status	Published - 2022 Oct

Bibliographical note

Funding Information:
This research was supported in part by the National Research Council of Science and Technology (NST) grant by the Korea government (MSIT) ( CAP-18014-000 ), the Technology Innovation Program ( 20014477 , Development of non-contact AI health monitoring system based on multimodal sensors) funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea), the Smart HealthCare Program ( www.kipot.or.kr ) ( 220222M0303 , Development and commercialization of police officer's life-log acquisition and stress/health management system through artificial intelligence based on big data analysis) funded by the Korean National Police Agency (KNPA, Korea), National Research Foundation of Korea (NRF) grants by the MSIT ( 2020M3A9I4038197 , and 2021R1C1C1005050 ), and KIST Intramural Grants ( 2E31121 ).

Publisher Copyright:
© 2022 The Authors

All Science Journal Classification (ASJC) codes

Pharmaceutical Science

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10.1016/j.jconrel.2022.09.008

Cite this

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title = "Cavitation-assisted sonothrombolysis by asymmetrical nanostars for accelerated thrombolysis",

abstract = "Sonothrombolysis with recombinant tissue plasminogen activator (rtPA) and microbubbles has been widely studied to enhance thrombolytic potential. Here, we report different sonothrombolysis strategy in nanoparticles using microbubbles cavitation. We found that different particles in shape exhibited different reactivity toward the cavitation, leading to a distinct sonothrombolytic potential. Two different gold nanoparticles in shape were functionalized with the rtPA: rtPA-functionalized gold nanospheres (NPt) and gold nanostars (NSt). NPt could not accelerate the thrombolytic potential with a sole acoustic stimulus. Importantly, NSt enhanced the potential with acoustic stimulus and microbubble-mediated cavitation, while NPt were not reactive to cavitation. Coadministration of NSt and microbubbles resulted in a dramatic reduction of the infarcts in a photothrombotic model and recovery in the cerebral blood flow. Given the synergistic effect and in vivo feasibility of this strategy, cavitation-assisted sonothrombolysis by asymmetrical NSt might be useful for treating acute ischemic stroke.",

author = "Wonseok Choi and Jaehong Key and Inchan Youn and Hyojin Lee and Sungmin Han",

note = "Funding Information: This research was supported in part by the National Research Council of Science and Technology (NST) grant by the Korea government (MSIT) ( CAP-18014-000 ), the Technology Innovation Program ( 20014477 , Development of non-contact AI health monitoring system based on multimodal sensors) funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea), the Smart HealthCare Program ( www.kipot.or.kr ) ( 220222M0303 , Development and commercialization of police officer's life-log acquisition and stress/health management system through artificial intelligence based on big data analysis) funded by the Korean National Police Agency (KNPA, Korea), National Research Foundation of Korea (NRF) grants by the MSIT ( 2020M3A9I4038197 , and 2021R1C1C1005050 ), and KIST Intramural Grants ( 2E31121 ). Publisher Copyright: {\textcopyright} 2022 The Authors",

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N1 - Funding Information: This research was supported in part by the National Research Council of Science and Technology (NST) grant by the Korea government (MSIT) ( CAP-18014-000 ), the Technology Innovation Program ( 20014477 , Development of non-contact AI health monitoring system based on multimodal sensors) funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea), the Smart HealthCare Program ( www.kipot.or.kr ) ( 220222M0303 , Development and commercialization of police officer's life-log acquisition and stress/health management system through artificial intelligence based on big data analysis) funded by the Korean National Police Agency (KNPA, Korea), National Research Foundation of Korea (NRF) grants by the MSIT ( 2020M3A9I4038197 , and 2021R1C1C1005050 ), and KIST Intramural Grants ( 2E31121 ). Publisher Copyright: © 2022 The Authors

PY - 2022/10

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N2 - Sonothrombolysis with recombinant tissue plasminogen activator (rtPA) and microbubbles has been widely studied to enhance thrombolytic potential. Here, we report different sonothrombolysis strategy in nanoparticles using microbubbles cavitation. We found that different particles in shape exhibited different reactivity toward the cavitation, leading to a distinct sonothrombolytic potential. Two different gold nanoparticles in shape were functionalized with the rtPA: rtPA-functionalized gold nanospheres (NPt) and gold nanostars (NSt). NPt could not accelerate the thrombolytic potential with a sole acoustic stimulus. Importantly, NSt enhanced the potential with acoustic stimulus and microbubble-mediated cavitation, while NPt were not reactive to cavitation. Coadministration of NSt and microbubbles resulted in a dramatic reduction of the infarcts in a photothrombotic model and recovery in the cerebral blood flow. Given the synergistic effect and in vivo feasibility of this strategy, cavitation-assisted sonothrombolysis by asymmetrical NSt might be useful for treating acute ischemic stroke.

AB - Sonothrombolysis with recombinant tissue plasminogen activator (rtPA) and microbubbles has been widely studied to enhance thrombolytic potential. Here, we report different sonothrombolysis strategy in nanoparticles using microbubbles cavitation. We found that different particles in shape exhibited different reactivity toward the cavitation, leading to a distinct sonothrombolytic potential. Two different gold nanoparticles in shape were functionalized with the rtPA: rtPA-functionalized gold nanospheres (NPt) and gold nanostars (NSt). NPt could not accelerate the thrombolytic potential with a sole acoustic stimulus. Importantly, NSt enhanced the potential with acoustic stimulus and microbubble-mediated cavitation, while NPt were not reactive to cavitation. Coadministration of NSt and microbubbles resulted in a dramatic reduction of the infarcts in a photothrombotic model and recovery in the cerebral blood flow. Given the synergistic effect and in vivo feasibility of this strategy, cavitation-assisted sonothrombolysis by asymmetrical NSt might be useful for treating acute ischemic stroke.

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Cavitation-assisted sonothrombolysis by asymmetrical nanostars for accelerated thrombolysis

Abstract

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