Figure 2. Schematic representation of nanocarriers for tPA-based nanothrombolysis.

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  Liposomes (A): tPA can be either incorporated into the inner core or adsorbed onto the outer shell of liposomes; tPA can bind to functionalized liposomes by covalent conjugation or by selective non-covalent metallochelation (His-tagged recombinant tPA);
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  Polymer-based nanoparticles (B): tPA can be encapsulated into PLGA or gelatin nanoparticles, and both nanoparticles can be furtherly coated with chitosan (red) or decorated with PEG or targeting moieties;
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  Magnetic nanoparticles (C): Most inner core of magnetic nanoparticles is iron oxide (Fe₃O₄ or γ-Fe₂O₃), and the surface is mostly coated with organic (e.g., dextran, polyacrylic acid, chitosan) or inorganic (SiO2) shell (yellow). tPA can bind to the shell with either COOH functional groups (blue) or -NH2 functional groups (blue);
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  Microbubbles (D–E): microbubbles are microspheres filled with gas (e.g., PFC), and are usually coated with albumin (grey, D) or phospholipids (blue, E) to increase the stability and facilitate tPA binding. When exposed to ultrasound, microbubbles can achieve site-specific delivery of tPA;
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  Echogenic liposomes (ELIP) (F): ELIP are liposomes with an outer phospholipid bilayer and a lipid monolayer shell surrounds a gas bubble in the inner aqueous compartment, gas can also locate between the lipid bilayers. tPA can be either incorporated into the inner aqueous compartment or adsorbed onto the outer phospholipid bilayer. Targeted release of tPA can be triggered by ultrasound.