Image by Andre E.X. Brown
Scientists say they have created drug-loaded nanocapsules that can target and destroy blood clots by exploiting the intrinsic properties of thrombosis.
These polymer capsules are “inherently responsive” to thrombus microenvironments.
They home to activated platelets, where exposure to thrombin prompts the capsules to degrade and release a thrombolytic drug—urokinase plasminogen activator—at the site of thrombosis.
Christoph Hagemeyer, PhD, of Baker IDI Heart and Diabetes Institute in Melbourne, Victoria, Australia, and his colleagues described the creation and testing of these capsules in Advanced Materials.
“We’ve created a nanocapsule that contains a clot-busting drug,” Dr Hagemeyer explained. “The drug-loaded nanocapsule is coated with an antibody that specifically targets activated platelets . . . .”
“Once located at the site of the blood clot, thrombin (a molecule at the center of the clotting process) breaks open the outer layer of the nanocapsule, releasing the clot-busting drug. We are effectively hijacking the blood-clotting system to initiate the removal of the blockage in the blood vessel.”
Specifically, Dr Hagemeyer and his colleagues created the capsules via layer-by-layer assembly of brushlike poly(2-ethyl-2-oxazoline) with alkyne functional groups on mesoporous silica particle templates.
The team loaded the capsules with the thrombolytic agent urokinase plasminogen activator and incorporated a thrombin-sensitive cross-linker to activate capsule degradation and drug release at the site of thrombosis.
So the capsules would target activated platelets, the researchers attached an antibody to the capsules’ surface. The team used a phage-display-derived single-chain antibody that is specific for the fibrinogen receptor GPIIb/IIIa in its activated form.
Flow chamber experiments showed that the capsules do target surface-bound GPIIb/IIIa receptors expressed on activated platelets.
And exposing the capsules to thrombin revealed concentration-dependent degradation and drug release. The researchers exposed loaded capsules to simulated thrombotic conditions with a range of thrombin concentrations.
In the presence of 1 unit mL−1, capsules degraded/released their cargo after 4 hours. With higher thrombin concentrations—5 or 10 units mL−1—capsules released their cargo within 15 minutes.
