Development of novel tumoral pH responsive nanoparticles for cancer therapy

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

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Summary
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.

 

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