2019 Fiscal Year Research-status Report
Reticuloendothelial system blockade by PEG-oligo(amino acid) block copolymers: A strategy for functional tuning of nanomedicine pharmacokinetics
| Project/Area Number |
18K18393
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| Research Institution | Kawasaki Institute of Industrial Promotion Innovation Center of NanoMedicine |
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Principal Investigator |
ディリサラ アンジャネユル 公益財団法人川崎市産業振興財団(ナノ医療イノベーションセンター), ナノ医療イノベーションセンター, 研究員 (70794353)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | Reticuloendothelium / Sinusoidal wall / Two-arm-PEG-OligoLysine / Liver blockade |
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| Outline of Annual Research Achievements |
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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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Progressing smoothly
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| Strategy for Future Research Activity |
Optimization of total PEG Mw will also be addressed in the future for further optimal tuning of the liver sinusoidal coating to maximize the efficacy of nanomedicine therapy, with minimal influence on liver physiological functions. The effect of sinusoidal wall coating by 2-arm-PEG－OligoLys with two strands of 80-kDa PEG (total PEG Mw per molecule is 160-kDa) vs. 1-arm-PEG-OligoLys with a single strand of 80-kDa PEG (total PEG Mw per molecule is 80-kDa) will be examined.
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| Causes of Carryover |
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Research Products
(4 results)
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[Journal Article] Single-Stranded DNA-Packaged Polyplex Micelle as Adeno-Associated-Virus-Inspired Compact Vector to Systemically Target Stroma-Rich Pancreatic Cancer2019
Author(s)
Theofilus A. Tockary, Wanling Foo, Anjaneyulu Dirisala, Qixian Chen, Satoshi Uchida, Shigehito Osawa, Yuki Mochida, Xueying Liu, Hiroaki Kinoh, Horacio Cabral, Kensuke Osada, Kazunori Kataoka
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Journal Title
ACS Nano
Volume: 13
Pages: 12732-12742
DOI
Int'l Joint Research
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