To provide long circulating nanoparticles which can carry a gene to tumors, we have designed anionic pegylated lipoplexes that are pH sensitive. Anionic pegylated lipoplexes have been prepared from the combined formulation of cationic lipoplexes and pegylated anionic liposomes. The neutralization of the particle surface charge as a function of the pH was monitored by light scattering, in order to determine the ratio between anionic and cationic lipids that would give pH sensitive complexes. This ratio has been optimized to form particles sensitive to pH change in the range 5.5-6.5. Compaction of DNA into these newly formed anionic complexes was checked by DNA accessibility to picogreen. The transfection efficiency and pH sensitive property of these formulations were shown in vitro using bafilomycin, a vacuolar H(+)-ATPase inhibitor.