Background: Recombinant tissue plasminogen activator (rtPA) has a short half-life, and additional hemorrhagic transformation (HT) can occur when treatment is delayed. Here, we report the design and thrombolytic performance of 3 μ m discoidal polymeric particles loaded with rtPA and superparamagnetic iron oxide nanoparticles (SPIONs), referred to as rmDPPs, to address the HT issues of rtPA. Methods: The rmDPPs consisted of a biodegradable polymeric matrix, rtPA, and SPIONs and were synthesized via a top-down fabrication. Results: The rmDPPs could be concentrated at the target site with magnetic attraction, and then the rtPA could be released under acoustic stimulus. Therefore, we named that the particles had magnetoacoustic properties. For the in vitro blood clot lysis, the rmDPPs with magnetoacoustic stimuli could not enhance the lytic potential compared to the rmDPPs without stimulation. Furthermore, although the reduction of the infarcts in vivo was observed along with the magnetoacoustic stimuli in the rmDPPs, more enhancement was not achieved in comparison with the rtPA. A notable advantage of rmDPPs was shown in delayed administration of rmDPPs at poststroke. The late treatment of rmDPPs with magnetoacoustic stimuli could reduce the infarcts and lead to no additional HT issues, while rtPA alone could not show any favorable prognosis. Conclusion: The rmDPPs may be advantageous in delayed treatment of thrombotic patients.
|Publication status||Published - 2022 Dec|
Bibliographical noteFunding 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), grant numbers 2018R1D1A1B07042339, and 2019K2A9A2A08000123.
© 2022, The Author(s).
All Science Journal Classification (ASJC) codes
- Ceramics and Composites
- Medicine (miscellaneous)
- Biomedical Engineering