Sequestering and inhibiting a vascular endothelial growth factor in vivo by systemic administration of a synthetic polymer nanoparticle

Hiroyuki Koide, Keiichi Yoshimatsu, Yu Hoshino, Saki Ariizumi, Anna Okishima, Takafumi Ide, Hiromichi Egami, Yoshitaka Hamashima, Yuri Nishimura, Hiroaki Kanazawa, Yoshiko Miura, Tomohiro Asai, Naoto Oku, Kenneth J. Shea

研究成果: ジャーナルへの寄稿記事

1 引用 (Scopus)

抄録

Protein affinity reagents (PARs), frequently antibodies, are essential tools for basic research, diagnostics, separations and for clinical applications. However, there is growing concern about the reproducibility, quality and cost of recombinant and animal-derived antibodies. This has prompted the development of alternatives that could offer economic, and time-saving advantages without the use of living organisms. Synthetic copolymer nanoparticles (NPs), engineered with affinity for specific protein targets, are potential alternatives to PARs. Although there are now a number of examples of abiotic protein affinity reagents (APARs), most have been evaluated in vitro limiting a realistic assessment of their potential for more demanding, practical in vivo applications. We demonstrate for the first time that an abiotic copolymer hydrogel nanoparticle (NP1) engineered to bind a key signaling protein, vascular endothelial growth factor (VEGF 165 ), functions in vivo to suppress tumor growth by regulating angiogenesis. Lightly cross-linked N-isopropylacrylamide based NPs that incorporate both sulfated N-acetylglucosamine and hydrophobic monomers were optimized by dynamic chemical evolution for VEGF 165 affinity. NP1 efficacy in vivo was evaluated by systemic administration to tumor-bearing mice. The study found that NP1 suppresses tumor growth and reduces tumor vasculature density. Combination therapy with doxorubicin resulted in increased doxorubicin concentration in the tumor and dramatic inhibition of tumor growth. NP1 treatment did not show off target anti-coagulant activity. In addition, >97% of injected NPs are rapidly excreted from the body following IV injection. These results establish the use of APARs as inhibitors of protein-protein interactions in vivo and may point the way to their broader use as abiotic, cost effective protein affinity reagents for the treatment of certain cancers and more broadly for regulating signal transduction.

元の言語英語
ページ(範囲)13-20
ページ数8
ジャーナルJournal of Controlled Release
295
DOI
出版物ステータス出版済み - 2 10 2019

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Nanoparticles
Vascular Endothelial Growth Factor A
Polymers
Proteins
Neoplasms
Doxorubicin
Growth
Chemical Evolution
Costs and Cost Analysis
Coagulants
Acetylglucosamine
Antibodies
Hydrogel
Signal Transduction
Therapeutics
Economics
Injections
Research
human VEGFA protein

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

これを引用

Sequestering and inhibiting a vascular endothelial growth factor in vivo by systemic administration of a synthetic polymer nanoparticle. / Koide, Hiroyuki; Yoshimatsu, Keiichi; Hoshino, Yu; Ariizumi, Saki; Okishima, Anna; Ide, Takafumi; Egami, Hiromichi; Hamashima, Yoshitaka; Nishimura, Yuri; Kanazawa, Hiroaki; Miura, Yoshiko; Asai, Tomohiro; Oku, Naoto; Shea, Kenneth J.

:: Journal of Controlled Release, 巻 295, 10.02.2019, p. 13-20.

研究成果: ジャーナルへの寄稿記事

Koide, H, Yoshimatsu, K, Hoshino, Y, Ariizumi, S, Okishima, A, Ide, T, Egami, H, Hamashima, Y, Nishimura, Y, Kanazawa, H, Miura, Y, Asai, T, Oku, N & Shea, KJ 2019, 'Sequestering and inhibiting a vascular endothelial growth factor in vivo by systemic administration of a synthetic polymer nanoparticle', Journal of Controlled Release, 巻. 295, pp. 13-20. https://doi.org/10.1016/j.jconrel.2018.12.033
Koide, Hiroyuki ; Yoshimatsu, Keiichi ; Hoshino, Yu ; Ariizumi, Saki ; Okishima, Anna ; Ide, Takafumi ; Egami, Hiromichi ; Hamashima, Yoshitaka ; Nishimura, Yuri ; Kanazawa, Hiroaki ; Miura, Yoshiko ; Asai, Tomohiro ; Oku, Naoto ; Shea, Kenneth J. / Sequestering and inhibiting a vascular endothelial growth factor in vivo by systemic administration of a synthetic polymer nanoparticle. :: Journal of Controlled Release. 2019 ; 巻 295. pp. 13-20.
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AU - Ide, Takafumi

AU - Egami, Hiromichi

AU - Hamashima, Yoshitaka

AU - Nishimura, Yuri

AU - Kanazawa, Hiroaki

AU - Miura, Yoshiko

AU - Asai, Tomohiro

AU - Oku, Naoto

AU - Shea, Kenneth J.

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