In this, study, we describe a multifunctional, nontoxic delivery vehicle with dual environment sensitivity to deliver plasmid DNA.(pDNA) into the cytoplasm of cells. This delivery vehicle was designed to be destabilized by reduction disulfide cross links in the intracellular environment and also to contain pH sensitive membrane destabilizing activity in acidic late endosomal/lysosomal compartments to allow escape of pDNA into the cell cytoplasm. Polyion complex formation was used to form ternary polyplexes using ionic polymers containing specific Chemistries to achieve functional demands. First, template binary polyplexes Were formed by association of cationic poly (L-lysine) containing thiol groups (PLys(PDP)) with pDNA and were subsequently cross-linked-by disulfide formation for increased stability Then, binary cross linked polyplexes were coated with a pH sensitive membrane active polyanion, Poly(ethylene glycol)-b-poly(aspartamide(DET Aco)) (PEG-PAsp(DET-Aco)), to produce ternary cross linked polyplexes. PEG-AsP(DET7-Aco) comprises two repeating units. of aminoethylene in PAsp side chains and primary amines modified with anionic cis-aconitic groups. PEG-PAsp(DET-Aco) degrades at acidic pH to generate the parent PEG-PAsp(DET) polymer, which is active toward late endosomal/lysosomal membranes and thus can assist in the endosomal escape Of pDNA following endocytosis. Binary/ternary cross-linked polyplexes remained stable toward counter polyanion exchange With dextral) sulfate, but released pDNA following disulfide reduction Ternary cross-linked polyplexes formed by addition. of PEG-PAsp(DET-ACo) resulted in enhanced gene transfection-efficieney in cultured cells (Huh-7 and HUVEC) without associated cytotoxicity. The-enhanced transfection was found to be correlated with improved endosomal escape by observation of intracellular trafficking using Confocal laser Scanning microscopy. This multifunctional ternary cross linked polyplex demonstrates the design of a gene delivery vehicle utilizing intracellular stimuli, and is a promising platform for further development toward practical use.