Co-delivery of paclitaxel and CXCL1 shRNA via cationic polymeric micelles for synergistic therapy against ovarian cancer

The preparation of polymer therapeutics capable of synergistic co-delivery systems for chemotherapeutic drugs and genes remains a tough problem in cancer therapy. Herein, we develop a novel co-delivery system for chemotherapeutic drugs and genes. Paclitaxel (PTX) was covalently grafted onto the cationic copolymer poly(ethylene glycol)- b -poly( l -lysine) (PEG- b -PLL) via a disulfide bond, and then CXCL1 shRNA was loaded on the cationic micelles PEG- b -PLL-SS-PTX by electrostatic interaction to construct PEG- b -PLL-SS-PTX/pDNA complex. The chemical structure of the complex was confirmed by gel permeation chromatography, 1 H NMR and Fourier transform infrared spectroscopy. The binding ability of the cationic micelles and pDNA was detected by gel retardation assay. In vitro gene transfection studies revealed an enhanced gene transfection efficiency due to the co-delivery of PTX and pDNA to ovarian cancer cells. In vitro and in vivo data demonstrated that the co-delivery complex exhibited a synergistic role of chemotherapy and gene therapy and possessed enhanced antitumor effects. The strategy of using drug-loaded cationic micelles as gene delivery carriers is a versatile approach to construct a co-delivery system, which might result in more efficient cancer therapy. © 2022 Society of Industrial Chemistry.