한빛사논문
Wonseok Choi 1 2, Hyeyoun Cho 2, Gahee Kim 2, Inchan Youn 1 3 4, Jaehong Key 5, Sungmin Han 6 7
1Biomedical Research Division, Korea Institute of Science and Technology, Seoul, Republic of Korea.
2Department of Biomedical Engineering, Yonsei University, Wonju, Republic of Korea.
3Divison of Bio-Medical Science & Technology, Korea Institute of Science and Technology School, Seoul, Republic of Korea.
4KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul, Republic of Korea.
5Department of Biomedical Engineering, Yonsei University, Wonju, Republic of Korea.
6Biomedical Research Division, Korea Institute of Science and Technology, Seoul, Republic of Korea.
7Divison of Bio-Medical Science & Technology, Korea Institute of Science and Technology School, Seoul, Republic of Korea.
Corresponding authors: Correspondence to Jaehong Key or Sungmin Han.
Abstract
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 μm 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.
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