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

doi:10.1016/j.jconrel.2017.10.028

Cited by 17 publications

(17 citation statements)

References 30 publications

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“…The HNP was formulated by optimizing the physiochemical properties by adjusting the anionic and hydrophobic monomer composition of the copolymer. Antibodies, synthetic polymers, and nanoparticles designed with the ability to sequester toxins responsible for sepsis pathology such as macrophage membrane coated nanoparticles 14 or synthetic copolymers 32 have also showed therapeutic effects for sepsis, validating this strategy as a potential therapeutic intervention. The success of these strategies is a function of many variables including their capacity for the target proteins which depends on in part surface area, a potential limitation to detoxi cation e ciency.…”

Section: Discussionmentioning

confidence: 96%

“…These features notwithstanding, a current challenge in HNP-based therapy has been their short circulation time in the blood 23,31 . One attempt to improve these involved conjugating histonecapturing synthetic linear copolymers to a lipid NP (a highly biocompatible drug delivery agent), improving the bloodstream circulation time following intravenous injection 32 . However, these lipid NPs had a low capture capacity and tended to aggregate after histone collection.…”

Section: Read Full License Introductionmentioning

confidence: 99%

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Synthetic hydrogel nanoparticles for sepsis therapy

Shea

Koide

Okishima

et al. 2021

Preprint

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Sepsis is a life-threatening condition caused by the extreme release of inflammatory mediators into the blood in response to infection (e.g., bacterial infection, COVID-19), resulting in the dysfunction of multiple organs. Currently, there is no direct treatment for sepsis. Here we report an abiotic hydrogel nanoparticle (HNP) as a potential therapeutic agent for late-stage sepsis. The HNP captures and neutralizes all variants of histones, a major inflammatory mediator released during sepsis. The highly optimized HNP has high capacity and long-term circulation capability for the selective sequestration and neutralization of histones. Intravenous injection of the HNP protected mice against a lethal dose of histones through the inhibition of platelet migration into the lungs. In vivo administration in murine sepsis model mice resulted in near complete survival. These results establish the potential for synthetic, nonbiological polymer hydrogel sequestrants as a new intervention strategy for sepsis therapy and adds to our understanding of the importance of histones to this condition.

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Section: Discussionmentioning

confidence: 96%

Section: Read Full License Introductionmentioning

confidence: 99%

Synthetic hydrogel nanoparticles for sepsis therapy

Shea

Koide

Okishima

et al. 2021

Preprint

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“…Taking advantage of sophisticated radical processes, such as atom transfer radical polymerization (ATRP) and reversible addition fragmentation chain transfer (RAFT) polymerization, multifunctional polymers with defined size distributions and sequences of functional groups have been prepared. Recently, controlled radical polymerization procedures have also been applied to the synthesis of polymer ligands with defined molecular weight distributions and localizations of functional groups that interact with target proteins and peptides . Haddleton et al.…”

Section: Methodsmentioning

confidence: 99%

Homogeneous Oligomeric Ligands Prepared via Radical Polymerization that Recognize and Neutralize a Target Peptide

et al. 2019

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Abiotic ligands that bind to specific biomolecules have attracted attention as substitutes for biomolecular ligands, such as antibodies and aptamers. Radical polymerization enables the production of robust polymeric ligands from inexpensive functional monomers. However, little has been reported about the production of monodispersed polymeric ligands. Herein, we present homogeneous ligands prepared via radical polymerization that recognize epitope sequences on a target peptide and neutralize the toxicity of the peptide. Taking advantage of controlled radical polymerization and separation, a library of multifunctional oligomers with discrete numbers of functional groups was prepared. Affinity screening revealed that the sequence specificity of the oligomer ligands strongly depended on the number of functional groups. The process reported here will become a general step for the development of abiotic ligands that recognize specific peptide sequences.

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“…There are some examples in which the inclusion of polyethylene glycol into NPs reduced the affinity for plasma proteins 44) and increased the circulation time. 45) However, polyethylene glycol (PEG) incorporation into NPs may also reduce the target affinity. Thus, we focused on a lipid nanoparticle (LNP), which is a highly biocompatible drug delivery agent, to improve the polymer circulation time after intravenous injection.…”

Section: Neutralizarion Of a Target Protein In The Bloodstream By Lipmentioning

confidence: 99%