Aptamers as Targeting Ligands in Thromboembolic Theranostics( I )

Plasminogen activator-induced thrombolysis is still the major strategy to restore blood flow and avoid tissue necrosis without requirement of surgical intervention in acute clinical setting. However, hemorrhagic adverse effects of the drug, recombinant tissue-type plasminogen activator (rtPA), limit its application. We have identified single strand DNA (ssDNA) sequence with high affinity to activated coagulation factor XIII (FXIIIa) using systematic evolution of ligands by exponential enrichment (SELEX) technology from ssDNA library; we thus hypothesize that this FXIIIa-specific aptamer may serve as an effective targeting ligand for both activated platelets and fibrin polymer in the thrombus. Three series of rtPA nanocomposites will be prepared and characterized, including magnetic nanoparticles (MNPs) with PLGA coating, Au nanoparticles-decorated graphene oxide nanocomposites and magnetoliposomes. The iron oxide-containing MNPs may also serve as contrast agents with magnetic resonance imaging at T2 mode; whereas Au nanoparticles may be visualized with computed tomography. This cross disciplinary team is composed of members with different expertise covering all areas required for this proposal. Experiments will be designed first, to develop FXIIIa-binding probes for thrombus imaging and targeting, and second, to develop FXIIIa-binding nanocomposites for targeted thrombolysis. Specific Aims are proposed:Aim 1- to optimize and characterize FXIII-targeting aptamersAim 2- to prepare and characterize FXIII-targeting nanocomposites for rtPA deliveryAim 3- to determine the thromolytic efficacy of the nanocompositesAim 4- to determine targeting/thrombolytic effects with MRI/CT

Project ID:PC10907-1584
External Project ID:MOST109-2124-M182-001