Hemocompatible pH-responsive polymeric nanoparticle for intravenous siRNA Delivery

摘要

We have synthesized and screened a library of pH-responsive polymers for formulation of in vivo-ready siRNA nanocarriers. The library was designed in order to optimize pH-dependent membrane disruptive activity for endosomal escape and stable siRNA packaging through balancing cationic and hydrophobic content of a core-forming block. PEG was used in the corona to impart hemocompatibilty and long circulation times. The most optimal polymer formulation is highly efficient at siRNA cytoplasmic delivery once internalized. Future work will investigate EPR-driven delivery to tumors in vivo and incorporation of cell-specific targeting ligands.