Virus-like particles with removable cyclodextrins enable glutathione-triggered drug release in cells.
The efficient delivery of hydrophobic drugs into target cells without the use of organic solvents or chemical linkage to delivery carriers is an important theme in the biomedical and pharmaceutical field. In this study, we synthesized virus-like particles (VLPs) coupled with cyclodextrins (CDs) as hydrophobic pockets through disulfide bonds inside the VLPs, where hydrophobic drugs can be incorporated. We report here the intracellular delivery of hydrophobic dyes or drugs encapsulated in VLPs through CDs with high efficiency and their subsequent release in cells in response to glutathione. As a model anticancer drug, paclitaxel (PTX)-CD complexes were encapsulated inside VLPs and the cytotoxic drug activity of PTX loaded VLPs against NIH3T3 cells was evaluated by CCK-8 assay. PTX-loaded VLPs exhibited a dose-dependent cytotoxic effect with a 20-fold smaller IC(50) than that of free PTX dissolved in DMSO. These results indicate that VLPs with removable CDs afford highly promising carriers of hydrophobic drugs without chemical modification of drugs.
Research Institute for Electronic Science (RIES), Hokkaido University, N21W10, Sapporo 001-0021, Japan. kniikura@poly.es.hokudai.ac.jp
Kenichi
K
Niikura
Naotoshi
N
Sugimura
Yusuke
Y
Musashi
Shintaro
S
Mikuni
Yasutaka
Y
Matsuo
Shintaro
S
Kobayashi
Keita
K
Nagakawa
Shuko
S
Takahara
Chie
C
Takeuchi
Hirofumi
H
Sawa
Masataka
M
Kinjo
Kuniharu
K
Ijiro
D000218:Adamantane / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism / Q000494:pharmacology; D001896:Boron Compounds / Q000737:chemistry / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003505:Cyclodextrins / Q000737:chemistry* / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D005978:Glutathione / Q000494:pharmacology*; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D007577:JC Virus / Q000737:chemistry; D051379:Mice; D041681:NIH 3T3 Cells; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D017239:Paclitaxel / Q000378:metabolism / Q000494:pharmacology; D010316:Particle Size; D012235:Rhodamines / Q000737:chemistry / Q000378:metabolism; D014771:Virion / Q000737:chemistry / Q000378:metabolism*
C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D000972:Antineoplastic Agents, Phytogenic; D001896:Boron Compounds; D003505:Cyclodextrins; D005456:Fluorescent Dyes; D053769:Nanocapsules; D012235:Rhodamines; D005978:Glutathione; D017239:Paclitaxel; D000218:Adamantane