Guanidine modified polyethyleneimine-g-polyethylene glycol nanocarriers for long interfering RNA (liRNA) based advanced anticancer therapy

Abstract

Combination therapy involving the synergism between different therapeutic approaches seems to be a promising strategy in anticancer treatment. Immunostimulatory long interfering RNA (liRNA) structures capable of executing specific RNA interference (RNAi) mediated gene silencing tasks seem to be potential candidates for a combination approach. Apart from their therapeutic efficacy, the unique structural format of liRNA candidates facilitates better association with cationic polymers and significantly improves their intra-cellular delivery. In this study, we have developed a biocompatible cationic delivery platform based on low molecular weight branched polyethyleneimine-grafted-polyethylene glycol (bPEI-g-PEG) for advanced liRNA based anticancer therapy. With simple guanidine (GU) modification, the bPEI-g-PEG platform could induce a strong RNAi mediated response in cancer cells, without induction of any obvious toxicity. Moreover, liRNA complexed with GU-bPEI-g-PEG which targets expression of Survivin gene sensitized cancer cells for effective chemotherapy. A combination strategy involving immunostimulatory RNAi mediators with conventional chemotherapeutic drugs seems to be an effective approach in advanced anticancer treatment.