S. Hama, S. Itakura, M. Nakai, K. Nakayama, S. Morimoto, H. Tsuchiya, K. Kogure
Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Kyoto, 607-8414, Japan
Novel charge-invertible nanoparticles were developed that can respond to the acidic pH of a tumor. We designed a unique peptide (referred to as a slightly acidic pH sensitive peptide: SAPSP), as a pH responsive device for intelligent nanoparticles consisting of cationic liposomes. The cellular uptake of SAPSP-modified liposomes (SAPSP-lipo) increased at tumoral pH (pH 6.5) due to conversion of the liposomal surface charge from negative to positive. The SAPSP-lipo were observed mainly in the cytosol after cellular internalization. In addition, siRNA-encapsulated SAPSP-lipo induced a significant knock down effect, but only at pH 6.5. These results indicate that SAPSP-lipo also have high functionality regarding endosomal escape. SAPSP-lipo represent a novel intelligent drug delivery system that can respond to tumoral pH for use in cancer therapy.