Figure 5.

Schematic illustration of the intracellular trafficking of mPEG-b-PLA-Phis-ssPEI and siRNA complexes. After internalized by tumor cell, (I) the complexes rapidly disassemble to release siRNA and free polyethylenimine (PEI) molecules in response to the acidic and reductive microenvironment, (II) efficiently escape from the endosome, facilitated simultaneously by cleaved PEI chains inducing membrane destabilization, the “proton sponge effect” of polyhistidine and polyethylenimine, as well as the relative small size of after disassembly, (III) achieve efficient gene silencing by cytosolic target mRNA cleavage. Adapted with permission from [179]. Copyright 2018 Elsevier.