Guanidine modified polyethyleneimine-g-polyethylene glycol nanocarriers for long interfering RNA (liRNA) based advanced anticancer therapyElectronic supplementary information (ESI) available: Supplementary data including, Quantification of degree of guanidination in bPEI-g-PEG, IC 50 values for Dox in HeLa/U87MG cells, NMR spectra of bPEI and bPEI-g-PEG, NC-3000 based quantification of liRNA uptake in U87MG using bPEI-g-PEG with varying degree of guanidination, liRNA induced toxicity under trans

• Main Authors: Sajeesh, S, Choe, Jeong Yong, Lee, Tae Yeon, Lee, Dong-ki
• Format: Article
• Language: English
• ISSN: 2050-750X; 2050-7518
• DOI: 10.1039/c4tb01621a

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. Long interfering RNA mediated advanced anticancer therapy.