Research & Publications
The ability to precisely control where drugs accumulate in the body after systemic administration would be transformative for treating a wide array of diseases from cancer to autoimmunity to organ rejection. Molecularly targeted nanomedicines (e.g. antibody-coated nanoparticles) were initially developed in the hope of realizing this anatomic precision to thereby significantly enhance efficacy and reduce toxicity. Unfortunately, multiple unsuccessful clinical trials have confirmed that we do not yet understand how to translate robust targeting in a petri dish into an effective therapeutic for a person. The two most significant impediments facing targeted nanomedicine are: 1) a lack of model systems with direct relevance to humans and 2) the lack of a theoretical framework to define the molecular properties necessary for therapeutically-relevant targeting. The recently developed clinical technique of Ex Vivo Normothermic Machine Perfusion (NMP), a method used to resuscitate and assess marginal organs during transplantation, provides a unique opportunity to overcome both these obstacles and thereby engineer a new generation of precision nanomedicines with direct translatability to man.
The central motivation of the Tietjen lab is to pioneer a synergistic bridge between nanotechnology and clinical organ transplant. More specifically, we aim to work directly with transplant clinicians to adapt ex vivo NMP in isolated organs for use as a model system to engineer vascular-targeted nanomedicines. Our work will emphasize the use of non-transplanted human organs to take advantage of the unique ability of NMP to provide a platform for preclinical, quantitative studies performed in viable human tissues. To maximize the experimental impact of each individual organ, we will develop a suite of integrated biophysical tools capable of real-time, 3D characterization of isolated organs undergoing NMP. The ultimate goal of the Tietjen lab is to use the NMP model to simultaneously develop new therapeutic/diagnostic paradigms for use in organ transplant, as well as to establish the theoretical foundation required for anatomic and cellular precision following systemic administration of targeted nanomedicines.