Quantitative modeling of cargo-carrier biogenesis for model-based design of drug-delivery systems

ended

Lipid-based drug delivery systems have shown great therapeutic potential, in particular for tumor targeting treatment. However, the production at relevant scales of such therapeutic agents remains a challenge due to the empirical nature of their development, and limited quantitative understanding of their biophysical properties. Remarkably, cells heavily utilize lipid carrier trafficking to encapsulate and transport with great efficiency various biological components to targeted sites in the intra- and extracellular environment. Inspired by the robustness of cellular trafficking processes, this proposal aims to elucidate the biophysical principles underlying the biogenesis of functional lipid carriers, and thereby direct the design and production of biomimetic transport carriers for drug delivery. Bringing together a complementary team of cell biologists, biophysicists, and mechanical engineers, we will develop a unifying modeling framework of vesicle biogenesis, in constant dialogue with experimental investigations of the mechanisms at play. The objectives of our integrated approach are two-fold: (i) elucidate the quantitative biophysical mechanisms of transport-carrier biogenesis mediated by coat proteins; and (ii) provide a toolbox for model-based design of liposome technologies for therapeutic drug delivery. All together, this project has potential impact in fundamental biology - by providing a systematic framework to formulate experimentally testable predictions and develop new ideas to control cellular functions in health and disease – as well as in biomedical engineering – by offering in silico solutions to design and test biomimetic cargo-carrier production processes for therapeutic applications.