Genetically multimodal therapy mediated by one polysaccharides-based supramolecular nanosystem.

Abstract

Multimodal therapy has been continuously explored for different diseases. Photodynamic/gene combined therapy is a promising treatment strategy of tumor. However, the limitation of traditional chemical photosensitizer and the asynchronism of the two therapies restrict the development of this technology. Herein, one genetically multimodal treatment nanosystem (HES@PGEA/pKR-p53), composed of biocompatible hydroxyethyl starch (HES), low-toxic β-cyclodextrin-based ethanolamine-functionalized poly(glycidyl methacrylate) (CD-PGEA) and combined plasmid pKR-p53, is structurally designed based on host-guest assembly and electrostatic complexing. Supramolecular assembled HES@PGEA exhibits low cytotoxicity, excellent cellular internalization and enhanced gene transfection efficiency. With the delivery of pKR-p53, p53 and KillerRed proteins could be expressed simultaneously in the same tumor cell for p53-mediated apoptosis therapy and photodynamic therapy (PDT), where the synergistic effect of KillerRed and p53 proteins is achieved. Compared with single therapy, HES@PGEA/pKR-p53 shows more remarkable antitumor effects in the 4T1 tumor model.