Rational designing of an antidote nanoparticle decorated with abiotic polymer ligands for capturing and neutralizing target toxins

Hiroyuki Koide, Hiroki Tsuchida, Masahiko Nakamoto, Anna Okishima, Saki Ariizumi, Chiaki Kiyokawa, Tomohiro Asai, Yu Hoshino, Naoto Oku

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Many of macromolecular toxins induce cell death by directly interacting with cells or induction of inflammatory cytokines. Abiotic polymer ligands (PLs) composed of functional monomers are able to bind and neutralize toxins in vivo and are of great interest for efficient antidotes. However, little has been reported about recognition and neutralization of target molecules in the bloodstream because of readily elimination from the bloodstream. Here, we report a rational design of PLs-decorated lipid nanoparticles (PL-NPs) for neutralizing a target toxin in vivo. PL that decorated on the NPs would cooperatively interacts with target biomacromolecules since the lipid molecules in NPs have a high degree of freedom. In the present study, N-isopropylacrylamide based PLs interacting with histones, major mediators of sepsis, were synthesized. Affinity between PL-NPs and histones depends on monomer composition and polymer length. The optimized PL-NP showed little affinity for plasma proteins. The PL-NPs inhibited the toxicity of histones both in vitro and in vivo, suggesting that PLs on the NPs cooperatively bound to histones and neutralized their toxicity. In addition, circulation time of optimized PL was significantly prolonged by the modification onto NPs. These results provide a platform for designing antidote nanoparticles neutralizing toxic biomacromolecules.

Original languageEnglish
Pages (from-to)335-342
Number of pages8
JournalJournal of Controlled Release
Volume268
DOIs
Publication statusPublished - Dec 28 2017

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Antidotes
Nanoparticles
Polymers
Ligands
Histones
Lipids
Poisons
Blood Proteins
Sepsis
Cell Death
Cytokines

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

Rational designing of an antidote nanoparticle decorated with abiotic polymer ligands for capturing and neutralizing target toxins. / Koide, Hiroyuki; Tsuchida, Hiroki; Nakamoto, Masahiko; Okishima, Anna; Ariizumi, Saki; Kiyokawa, Chiaki; Asai, Tomohiro; Hoshino, Yu; Oku, Naoto.

In: Journal of Controlled Release, Vol. 268, 28.12.2017, p. 335-342.

Research output: Contribution to journalArticle

Koide, Hiroyuki ; Tsuchida, Hiroki ; Nakamoto, Masahiko ; Okishima, Anna ; Ariizumi, Saki ; Kiyokawa, Chiaki ; Asai, Tomohiro ; Hoshino, Yu ; Oku, Naoto. / Rational designing of an antidote nanoparticle decorated with abiotic polymer ligands for capturing and neutralizing target toxins. In: Journal of Controlled Release. 2017 ; Vol. 268. pp. 335-342.
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