Multi-functional carriers for intracellular protein drugs have been developed that enhance endosomal release and cytosolic delivery to disease targets.  The carrier systems are designed to mechanistically mimic pathogenic delivery systems that have evolved remarkably efficient cytosolic delivery capabilities. After internalization into vesicular compartments, the pH drops during endosomal-lysosomal development, triggering exposure of a membrane-destabilizing domain in viral proteins such as hemagluttinin or pathogenic proteins such as diphtheria toxin. The ampholytic carriers are designed like these pathogens to activate via protonation events triggered in the endosome.  This endosomal-releasing activity is then built into a multi-functional polymer platform that incorporates targeting elements, conjugation or complexation elements, and a �stealth� component to optimize safety and pharmaco-kinetic properties. Initial studies have shown these carriers can suppress tumor growth and prolong survival in human lymphoma disease models.

Dynamic carrier systems for protein drug delivery

248th National Meeting (2014)

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