Abstract
Cationic polymers are important vectors for gene transfection, but the paradox between high transfection efficacy and low toxicity is always a hindrance to their applications in gene therapy. Here, we developed a core-shell polyplex using a high generation dendrimer to condense plasmid DNA at a very low nitrogen/phosphorus (N/P) ratio, followed by coating with a low-molecular-weight cationic polymer to offset the positive charge. Different high generations of polyamidoamine (PAMAM) dendrimers as core polymers and low-molecular-weight linear polyethylenimine (LPEI), branched PEI and G2 PAMAM dendrimer as shell polymers were tested. Among them, the polyplex composed of G8 PAMAM dendrimer and LPEI (G8/LPEI/DNA) at a core N/P ratio of 0.25 and a shell N/P ratio of 100 exhibited the highest transfection efficacy and minimal toxicity. The mechanism investigation indicated that the G8/LPEI/DNA polyplex possessed an incompact structure that facilitated DNA release in the cytoplasm. Our study provides an ingenious approach for high efficiency and low toxicity gene transfection.
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