Assembly, Dosimetry, and Assessment of a Platform Technology for the Delivery of Thrombolytics

Project Summary The proposed research seeks to validate and extend a platform technology for the delivery of protein-based drugs, which includes application to current and next generation therapeutics. The bioengineering strategy employs the designed assembly of endogenous biomolecules, namely thrombolytic enzymes and vitamin B12, as well as cell-based transport and delivery to create a biocompatible drug delivery platform. The drug delivery technology uses the circulatory system as a natural drug depot, is drug agnostic, releases the protein therapeutic at the diseased site in a photon-targeted fashion, and is 25-fold more effective than the standard of care in our preliminary in vivo studies. The wavelength of drug release is readily assigned at the molecular level. The following issues will be addressed: (i) accommodation of an array of thrombolytic proteins that operate by distinct mechanisms; (ii) multi-drug synergism of thrombolysis (iii) responsiveness to deep tissue penetrating photons; (iv) delivery efficacy as a function of irradiation parameters, melanin and body mass index, and sex; and (v) therapeutic efficacy and safety under conditions in which therapy is contraindicated.