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 Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 90120:Biomaterials-related
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| Research Institution | Kawasaki Institute of Industrial Promotion Innovation Center of NanoMedicine |
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Principal Investigator |
Dirisala Anjaneyulu 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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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | RES blockade / PEG coating to liver / Two-arm-PEG-peptide / Bile clearance / Retargeting nanomedicine / Reticuloendothelium / Sinusoidal wall / Two-arm-PEG-OligoLysine / Liver blockade / Single arm PEG-OLys / Double arm PEG-OLys / PEG-oligo(amino acid) |
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| Outline of Final Research Achievements |
A single biggest issue of systemically injected nanomedicines is nonspecific elimination by the liver sinusoidal wall cells, which substantially decrease the delivery efficiency at diseased sites. We addressed this issue by stealth coating of liver sinusoidal wall using single- or two-armed poly(ethylene glycol) (PEG)-conjugated oligo(l-lysine)(OligoLys). PEG-OligoLys selectively coated to the liver sinusoidal wall, leaving the other tissue endothelium uncoated and, thus, accessible to the nanomedicine delivery. Interestingly, 2-arm-PEG-OligoLys uncoated the sinusoidal wall within hours and cleared to the bile, while 1-arm-PEG-OligoLys persisted at the wall. Such transient and selective stealth coating of sinusoidal wall by two-arm-PEG-OligoLys was effective in preventing the sinusoidal clearance of nonviral and viral gene vectors, representatives of synthetically-engineered and nature-derived nanomedicines, respectively, thereby boosting their gene transduction at the diseased sites.
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| Academic Significance and Societal Importance of the Research Achievements |
Our transient and selective stealth coating strategy is expected to (i) improve the efficacy of gene therapy drugs, (ii) reduce the dose required to obtain therapeutic outcomes, and (iii) decrease dose-related toxicities, which ultimately lead to the reduction of the medical cost of nanomedicines.
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Report
(4 results)
Research Products
(14 results)
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[Journal Article] Dual-Sensitive Nanomicelles Enhancing Systemic Delivery of Therapeutically Active Antibodies Specifically into the Brain2020
Author(s)
Jinbing Xie, Daniel Gonzalez-Carter, Theofilus A. Tockary, Noriko Nakamura, Yonger Xue, Makoto Nakakido, Hiroki Akiba, Anjaneyulu Dirisala, Xueying Liu, Kazuko Toh, Tao Yang, Zengtao Wang, Shigeto Fukushima, Junjie Li, Sabina Quader, Kouhei Tsumoto, Takanori Yokota, Yasutaka Anraku*, and Kazunori Kataoka
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Journal Title
ACS Nano
Volume: -
Issue: 6
Pages: 6729-6742
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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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 cancer.2019
Author(s)
T. A. Tockary, W. Foo, A. Dirisala, Q. Chen, S. Uchida, S. Osawa, Y. Mochida, X. Liu, H. Kinoh, H. Cabral, K. Osada, K. Kataoka
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Journal Title
ACS Nano
Volume: 13
Issue: 11
Pages: 12732-12742
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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