Intracellular release of rapamycin from poly (lactic acid) nanospheres modifies autophagy.
The objective of this study is to investigate the autophagy activity of cells by the intracellular release of rapamycin (Rapa) of an autophagy inducer. Rapa was incorporated into nanospheres of poly (lactic-co-glycolic acid) (PLGA) for the controlled release of Rapa. Rapa was released from the PLGA nanospheres incorporating rapamycin (Rapa-PLGA-NS) with time while the Rapa-PLGA-NS were hydrolytically degraded. When human hepatocellular carcinoma (HepG2) cells were incubated with the Rapa-PLGA-NS, the Rapa-PLGA-NS were internalized, and the intracellular concentration was maintained over four days, indicating the intracellular Rapa release. The microtubule-associated protein 1 light chain (LC3) of an autophagy marker was significantly high for the Rapa-PLGA-NS group compared with the free Rapa group even after four days incubation. In addition, intracellular harmful ubiquitinated proteins were degraded by the intracellular release of Rapa even after four days incubation in contrast to free Rapa. It is concluded that the intracellular Rapa release is effective in modulating the autophagy activity over a longer time period.
a Department of Biomaterials, Field of Tissue Engineering , Institute for Frontier Medical Sciences, Kyoto University , Kyoto , Japan.
Junpei
J
Nagata
a Department of Biomaterials, Field of Tissue Engineering , Institute for Frontier Medical Sciences, Kyoto University , Kyoto , Japan.
Makoto
M
Matsui
a Department of Biomaterials, Field of Tissue Engineering , Institute for Frontier Medical Sciences, Kyoto University , Kyoto , Japan.
Yasuhiko
Y
Tabata
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects*; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D056945:Hep G2 Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D007976:Leupeptins / Q000494:pharmacology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D054118:Nanospheres / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D061988:Proteasome Inhibitors / Q000494:pharmacology; D020123:Sirolimus / Q000737:chemistry* / Q000494:pharmacology; D013499:Surface Properties
D000970:Antineoplastic Agents; D004337:Drug Carriers; D007976:Leupeptins; D008869:Microtubule-Associated Proteins; D061988:Proteasome Inhibitors; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D020123:Sirolimus
Autophagy; PLGA; intracellular sustained release; nanosphere