Figure 1.

A two agent intracellular delivery system. The central concept of this work is that independently targeted, membrane disrupting functionality can be delivered to tumor cells via Fn3-cytolysin fusions. Simultaneous targeted delivery of such a Potentiator to tumor cells that internalize by endocytosis an independently targeted Biotherapeutic will potentiate the therapeutic effect by improving escape to the cytoplasm, the site of action. By separating the membrane-crossing and therapeutic components, we are able to dramatically improve specificity and potency. The traditional fate of intracellularly active biotherapeutics (a) leads to degradation in the lysosome, but upon compartmental colocalization of biotherapeutic and potentiator (b), the lysin's membrane disruptive characteristics facilitate therapeutic access the cytoplasm