| Project/Area Number |
26870301
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Applied pharmacology
Biomedical engineering/Biomaterial science and engineering
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| Research Institution | Kyoto University |
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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)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | endosomal escape / internalization / membranolytic polymer / anticancer drug delivery / mildy acidic pH / high-density lipoprotein / anionic polymer / cell-penetrating peptide / drug delivery |
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| 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.
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