Hongmei Li, Shann S. Yu, Martina Miteva, Christopher E. Nelson, Thomas Werfel, Todd D. Giorgio and Craig L. Duvall Matrix Metalloproteinase Responsive, Proximity-Activated Polymeric Nanoparticles for siRNA Delivery Advanced Functional Materials 23
A pH-responsive, smart polymeric nanocarrier (SPN) with matrix metalloproteinase (MMP)-7-dependent proximity-activated targeting (PAT) incorporates polyethylene glycol (PEG) shielding that is removable in MMP-7-rich environments (e.g., breast cancer metastases). The up-regulated MMP-7 activity in pathological tissue exposes the cationic component of the SPN polymer, triggering cell uptake. Following internalization of polymers into the endosomal pathway, pH-dependent endosomal escape facilitates cytosolic siRNA delivery.
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