Scheme 1.
Multistage pH-responsive co-delivery liposome and its tumor-targeted delivery strategy. a The acidic pHe in the tumor microenvironment splits DPRP at the imine site and detaches the shielding domain from the CPP section, thereby recovering the potency of CPP for enhanced cellular internalization and endosome/lysosome escape. b In the acidic environment of endosomes/lysosomes (pH 5.0–6.0), the anionic siRNA forms a complex with the cationic SA-H8 by electrostatic interactions. When the complexed siRNA delivered to cytoplasm (pH 7.4), histidines in SA-H8 undergo transformation into their uncharged form, resulting in the dissociation of the complex and efficient release of siRNA