Article ; Online: A bioinspired hyperthermic macrophage-based polypyrrole-polyethylenimine (Ppy-PEI) nanocomplex carrier to prevent and disrupt thrombotic fibrin clots.
2019 Volume 96, Page(s) 468–479
Abstract: ... technology using macrophages loaded with polypyrrole-polyethylenimine nanocomplexes (Ppy-PEI NCs) and ... subjected to near-infrared radiation (NIR). We first show that the developed Ppy-PEI NCs could be taken up ... by defensive macrophages in vitro through endocytosis. The Ppy-PEI NCs generated local hyperthermia upon NIR ...
| Abstract | Fibrinolytic treatments for venous or arterial thrombotic syndromes using systemic administration of thrombolytics, such as streptokinase, can induce life-threatening bleeding complications. In this study, we offer the first proof of concept for a targeted photothermal fibrin clot prevention and reduction technology using macrophages loaded with polypyrrole-polyethylenimine nanocomplexes (Ppy-PEI NCs) and subjected to near-infrared radiation (NIR). We first show that the developed Ppy-PEI NCs could be taken up by defensive macrophages in vitro through endocytosis. The Ppy-PEI NCs generated local hyperthermia upon NIR treatment, which appeared to produce reactive oxygen species in Ppy-PEI NC-loaded macrophages. Preliminary evidence of efficacy as an antithrombotic tool is provided, in vitro, using fibrinogen-converted fibrin clots, and in vivo, in a rat femoral vascular thrombosis model generated by exposure to ferric chloride substance. The in vivo biocompatibility, photothermal behavior, biodistribution, and histological observation of cellular interactions with the Ppy-PEI NCs in the rat model provide rationale in support of further preclinical studies. This Ppy-PEI NC/NIR-based method, which uses a unique macrophage-guided targeting approach to prevent and lyse fibrin clots, may potentially overcome some of the disadvantages of current thrombolytic treatments. STATEMENT OF SIGNIFICANCE: Fibrinolytic treatments for venous or arterial thrombotic syndromes using systemic administration of thrombolytics, such as streptokinase, can induce life-threatening bleeding complications. In this study, we offer the first proof of concept for a targeted photothermal fibrin clot reduction technology using macrophages loaded with polypyrrole-polyethylenimine nanocomplexes (Ppy-PEI NCs) and subjected to near-infrared radiation (NIR). We first show that the developed Ppy-PEI NCs can be taken up by defensive macrophages in vitro through endocytosis. The Ppy-PEI NCs generated local hyperthermia upon NIR treatment, which appeared to produce reactive oxygen species in Ppy-PEI NC-loaded macrophages. Preliminary evidence of efficacy as an antithrombotic tool is provided, in vitro, using fibrinogen-converted fibrin clots, and in vivo, in a rat femoral vascular thrombosis model generated by exposure to ferric chloride substance. The in vivo biocompatibility, photothermal behavior, biodistribution, and histological observation of cellular interactions with the Ppy-PEI NCs in the rat model provide rationale in support of further preclinical studies. This Ppy-PEI NC/NIR-based method, which uses a unique macrophage-guided targeting approach to disintegrate fibrin clots, may potentially overcome some of the disadvantages of current thrombolytic treatments. |
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| MeSH term(s) | Animals ; Biomimetic Materials/chemistry ; Endocytosis ; Fibrin/metabolism ; Humans ; Hyperthermia, Induced ; Infrared Rays ; Macrophages/cytology ; Mice ; Mice, Inbred ICR ; Nanoparticles/chemistry ; Nanoparticles/ultrastructure ; Polyethyleneimine/pharmacology ; Polymers/pharmacology ; Pyrroles/pharmacology ; RAW 264.7 Cells ; Reactive Oxygen Species/metabolism ; Temperature ; Thrombosis/prevention & control ; Tissue Distribution |
| Chemical Substances | Polymers ; Pyrroles ; Reactive Oxygen Species ; polypyrrole (30604-81-0) ; Fibrin (9001-31-4) ; Polyethyleneimine (9002-98-6) |
| Language | English |
| Publishing date | 2019-06-29 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2173841-5 |
| ISSN | 1878-7568 ; 1742-7061 |
| ISSN (online) | 1878-7568 |
| ISSN | 1742-7061 |
| DOI | 10.1016/j.actbio.2019.06.053 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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