The gene transfection efficiency of a folate–PEI600–cyclodextrin nanopolymer

Abstract The success of gene therapy relies on a safe and effective gene delivery system. In this communication, we describe the use of folate grafted PEI 600 –CyD (H 1 ) as an effective polyplex-forming plasmid delivery agent with low toxicity. The structures of the polymer and polyplex were characterized, and the in vitro transfection efficiency, cytotoxicity, and in vivo transfection of H 1 were examined. We found that folate molecules were successfully grafted to PEI 600 –CyD. At N / P ratios between 5 and 30, the resulting H 1 /DNA polyplexes had diameters less than 120 nm and zeta potentials less than 10 mV. In various tumor cell lines examined (U138, U87, B16, and Lovo), the in vitro transfection efficiency of H 1 was more than 50%, which could be improved by the presence of fetal bovine serum or albumin. The cytotoxicity of H 1 was significantly less than high molecular weight PEI-25 kDa. Importantly, in vivo optical imaging showed that the efficiency of H 1 -mediated transfection (50 μg luciferase plasmid (pLuc), N / P ratio = 20/1) was comparable to that of adenovirus-mediated luciferase transduction (1 × 10 9  pfu) in melanoma-bearing mice, and it did not induce any toxicity in the tumor tissue. These results clearly show that H 1 is a safe and effective polyplex-forming agent for both in vitro and in vivo transfection of plasmid DNA and its application warrants further investigation.