Cancer Therapy: Esterase‐Activated Charge‐Reversal Polymer for Fibroblast‐Exempt Cancer Gene Therapy (Adv. Mater. 48/2016)

Abstract

An esterase-responsive charge-reversal polymer (ERP) was designed whose polyplexes had a selective gene expression in the cancer cells high in esterases, but conserved fibroblasts owing to their low esterase activity. Such polyplexes carrying TRAIL plasmids effectively induced apoptosis of HeLa cells but did not activate fibroblasts to secrete WNT16B, enabling the TRAIL gene therapy to exert potent anticancer activity with few side effects. This overcomes the common problem of chemotherapy drugs, which indiscriminately kill and damage fibroblasts activating them to secrete WNT16B that stimulates the surviving cancer cells to be drug resistant and metastatic. The work demonstrates a novel approach to selective gene expression in cells via responsive dissociation of polyplexes triggered by intracellular signals.