Mixed anionic and cationic polyphosphazene complexes for effective gene delivery to glioblastoma in vitro and in vivo

Abstract

Here we describe an approach to such vectors, using new variants of polyphosphazene materials and describe the synthesis of a series of degradable polyphosphazenes with both cationic and anionic side-chains, and report their use as mixed polyelectrolyte complexes for DNA and RNA delivery to glioblastoma cells in vitro and in vivo. Transfection assays in 3D spheroid models and in subcutaneous xenograft U87MG tumours confirmed higher transgene expression for these mixed cationic and anionic poly(phosphazene)s compared to the related poly(alkylamino-phosphazene)-DNA complexes, and also to PEI-DNA complexes. Extension of the approach to siRNA delivery showed that the mixed cationic and anionic poly(phosphazene)s were able to silence a gene encoding for a kinase implicated in tumour progression (DYRK1A), resulting in a reduced renewal ability of U87MG cells in vitro and in delay of tumour growth in a xenograft model.