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- Title
Targeted Thrombolysis with Magnetic Nanotherapeutics: A Translational Assessment.
- Authors
Lin, Ming-Lu; Wu, Siao-Yun; Chen, Jyh-Ping; Lu, Yi-Ching; Jung, Shih-Ming; Wey, Shiaw-Pyng; Wu, Tony; Ma, Yunn-Hwa
- Abstract
Plasminogen activators, such as recombinant tissue-type plasminogen activators (rtPAs), while effective in treating thromboembolic diseases, often induce hemorrhagic complications due to non-specific enzyme activities in the systemic circulation. This study evaluated the targeting efficiency, efficacy, biodistribution, and potential toxicity of a rtPA covalently attached to chitosan-coated magnetic nanoparticles (chitosan-MNP-rtPA). The thrombolytic activity of a chitosan-MNP-rtPA was preserved by protection from an endogenous plasminogen activator inhibitor-1 (PAI-1) in whole blood and after circulation in vivo, as examined by thromboelastometry. Single-photon emission computed tomography (SPECT) demonstrated real-time retention of a 99mTc-MNP-rtPA induced by magnet application in a rat embolic model; an 80% reduction in rtPA dosage for a chitosan-MNP-rtPA with magnetic guidance was shown to restore blood flow. After treatment, iron deposition was observed in the reticuloendothelial systems, with portal edema and neutrophil infiltration in the liver at a ten-fold higher dose but not the regular dose. Nevertheless, no liver or renal toxicity was observed at this higher dose. In conclusion, the liver may still be the major deposit site of rtPA nanocomposites after targeted delivery; chitosan-coated MNPs are potentially amenable to target therapeutics with parenteral administration.
- Subjects
TISSUE plasminogen activator; SINGLE-photon emission computed tomography; PLASMINOGEN activators; PARENTERAL therapy; RETICULO-endothelial system
- Publication
Pharmaceutics, 2024, Vol 16, Issue 5, p596
- ISSN
1999-4923
- Publication type
Article
- DOI
10.3390/pharmaceutics16050596