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 intracellular 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.