Potential of pH-sensitive polymer-anchored cationic liposomes for combinatorial anticancer therapy with doxorubicin and siRNA

Abstract

To explore a potential of pH-sensitive polymer-liposome complexes for the tumor-specific combinatorial delivery of anticancer agents and siRNA, conventional liposomes (ConL), polymer-liposome complexes (PLC) and polymer-cationic liposome complexes (PCLC) were prepared. Pluronic P104-based multiblock copolymer (MBCP-2) was included as pH-sensitive polymer. Physicochemical properties, release under different pH, cytotoxicity and in vitro cellular uptake of DOX-loaded liposomes were investigated. From the release test, an acidic pH was determined to be an important factor for release from the PLC vehicles. The novel PLC vehicle itself showed low cytotoxicity demonstrating suitable viability,. Observing cellular uptake of DOX by confocal microscopy imaging, a greater amount of DOX was delivered to cells with the pH-sensitive polymer-anchored vehicles than that with free DOX and ConL. It was verified that the novel vehicles could effectively deliver both DOX and GFP-siRNA. Novel pH-sensitive PCLC have a potential for targeted therapy of anticancer agents and gene therapy under acidic tumor microenvironment.