Abstract
This paper features the synthesis of thrombin-responsive, nucleic acid-gated, UiO-68 metal–organic framework nanoparticles (NMOFs) loaded with the drug Apixaban or rhodamine 6G as a drug model. Apixaban acts as an inhibitor of blood clots formation. The loads in the NMOFs are locked by duplex nucleic acids that are composed of anchor nucleic acids linked to the NMOFs that are hybridized with the anti-thrombin aptamer. In the presence of thrombin, the duplex gating units are separated through the formation of thrombin–aptamer complexes. The unlocking of the NMOFs releases the drug (or the drug model). The release of the drug is controlled by the concentration of thrombin. The Apixaban-loaded NMOFs revealed improved inhibition, as compared to free Apixaban, toward blood clot formation. This is reflected by their longer time intervals for inducing clot formation and the decreased doses of the drug required to affect clots formation. The beneficial effects of the Apixaban-loaded NMOFs are attributed to the slow-release mechanism induced by the NMOFs carriers, where the inhibition of factor Xa in the blood clotting cycle retards the formation of thrombin, which slows down the release of the drug.
Highlights
Metal–organic framework nanoparticles (NMOFs) represent a broad class of porous nanostructures [1,2,3,4]
We have shown that the drug-loaded NMOFs can be Sensors 2019, 19, 5260; doi:10.3390/s19235260
The loading of the nucleic acid (1) was evaluated spectroscopically, and it corresponded to 9.4 nmol/mg of NMOFs
Summary
Metal–organic framework nanoparticles (NMOFs) represent a broad class of porous nanostructures [1,2,3,4]. Different triggers, such as pH [26], light [27], heat [28], catalytic nucleic acids [29], chemical reagents [30], and aptamer–ligand complexes [31], were used to unlock the carriers and release the loads Within these broad efforts, the use of nucleic acid-gated, drug-loaded, metal–organic framework nanoparticles (NMOFs) acting as stimuli-responsive carriers [32,33] was recently demonstrated by our laboratory. The stimuli-responsive NMOFs acts as functional thrombin sensors that lead to the autonomous unlocking of the gated NMOFs, which is a process that activates the release of the anti-clotting drug. We combine the thrombin aptamer units in the NMOFs as functional stimuli-responsive gates that allow the thrombin-triggered release of the anti-blood clotting drug from the NMOFs carriers. We present a means to control the anti-blood clotting process by the natural blood clotting cycle
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