Development of endosomal membrane destabilizing high-density lipoprotein nanoparticle using pH-responsive polymer

2015 Fiscal Year Final Research Report

• Project/Area Number: 26870301
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied pharmacology; Biomedical engineering/Biomaterial science and engineering
• Research Institution: Kyoto University
• Principal Investigator: KIM HYUNGJIN 京都大学, 物質ー細胞統合システム拠点, 特定研究員 (80711457)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: endosomal escape / internalization / membranolytic polymer / anticancer drug delivery / mildy acidic pH

Outline of Final Research Achievements

Intracellular drug delivery by nanoparticles is often hampered by their endosomal entrapment followed by their degradation in the lysosomal compartment and/or exocytosis. Here, we show that internalization and endosomal escape of cargoes in a cationized natural nanocarrier, high-density lipoprotein (HDL), can be controlled in a pH-dependent manner through stable complexation with a membranolytic anionic block polymer. A genetically and chemically cationized form of HDL (catHDL) is prepared. Upon addition of polyanion (PA), catHDL yields inhibition of internalization at neutral pH and its subsequent recovery at mildly acidic pH. Significant enhancement of endosomal escape of a catHDL component is observed after a 1h treatment of human cancer cells with catHDL/PA. Anti-cancer drugs, encapsulated into catHDL/PA are also translocated outside of endosomes, compared with that into catHDL, and their cytotoxicities are enhanced inside the cells.

Free Research Field

drug delivery