Gene therapy emerged as a promising treatment option for acquired and inherited diseases. The delivery of nucleic acids relies on vectors that condense and encapsulate their cargo. Especially non-viral gene delivery systems are of increasing interest. However, accomplishing therapeutic transgene expression levels and limited tolerability of these systems remain a challenge. Therefore, we investigate in the improvement of nucleic acid delivery using depolymerized chitosan – polyethylenimine DNA complexes (dCS-PEI/DNA). These core complexes are further entrapped into chitosan-based shells, functionalized with polyethylene glycol and cell penetrating peptides. This modular approach allows to evaluate the effect of functional shell components on physico-chemical particle characteristics and biological effects. The optimized ternary complex combines a core-dCS-LPEI/DNA complex with a shell consisting of dCS-PEG-COOH, which resulted in improved nucleic acid encapsulation, cellular uptake, transfection efficiency, and transfection potency in human hepatoma HuH-7 cells and murine primary hepatocytes. Effects on transgene expression are confirmed in wild-type mice following retrograde intrabiliary infusion. After administration of only 100 ng complexed DNA, ternary complexes induce a high reporter gene signal for three days. We conclude that ternary core-shell structured particles comprising functionalized chitosan are a promising gene delivery technology for both in vitro as well as in vivo applications.