Cavitation-assisted sonothrombolysis by asymmetrical nanostars for accelerated thrombolysis

• Published in: Journal of controlled release 2022-10, Vol.350, p.870-885
• Main Authors: Choi, Wonseok, Key, Jaehong, Youn, Inchan, Lee, Hyojin, Han, Sungmin
• Format: Article
• Language: English
• Subjects: acoustics; Asymmetrical gold Nanostars; blood flow; Cavitation; gold; microbubbles; nanogold; nanoparticles; nanospheres; Sonothrombolysis; stroke; synergism; Synergistic therapeutic effect; t-plasminogen activator
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2022.09.008

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. [Display omitted] •We developed asymmetrical NSt through electrostatic interactions between NS and rtPA.•We reacted the NSt with various reagents used in sonothrombolysis (e.g., rtPA and microbubbles) and compared the synergistic sonothrombolytic potential.•NSt improved sonothrombolytic potential in vitro and ischemic stroke symptom relief in vivo.•NSt might offer the potential for effective sonothrombolysis in treating time-sensitive thrombotic diseases.