| 研究実績の概要 |
The liver sinusoidal endothelium nonspecifically sequesters the systemically administered nanomedicines, even though shielded with nonionic stealth materials. This clearance substantially decreases the delivery amount of nanomedicines at the targeted site. Here, this issue is addressed by in situ stealth coating of sinusoidal wall using poly(ethylene glycol) (PEG)-block-OligoLysine (PEG－OligoLys). In this study, two types of PEG－OligoLys were used using either a single linear 80-kDa PEG (1-armed) or double linear chains of 40-kDa PEG (2-armed) (2 × 40-kDa each arm = 80-kDa). Both 1- and 2-arm-PEG－OligoLys selectively coated to the liver sinusoidal wall, leaving the endothelium of other tissues uncoated and thus accessible to the nanomedicines. Interestingly, 2-arm-PEG－OligoLys was cleared from sinusoidal wall to the bile within hours, while 1-arm-PEG－OligoLys persisted at the sinusoidal wall, indicating the 2-arm-PEG－OligoLys would be useful for transient coating of the sinusoidal wall. Such transient and selective stealth coating of liver sinusoids by 2-arm-PEG－OligoLys was finally used for preventing the sinusoidal clearance of both non-viral and viral gene drug delivery systems and successfully relocated these nanomedicines to their targeted sites and resulted in an increased gene transfection efficiency.
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