Citrullinated peptide epitope targets therapeutic nanoparticles to human neutrophils

Sangita Khatri, Jonas Hansen, Ana Carina Loureiro Mendes, Ioannis S. Chronakis, Shu-Chen Hung, Elizabeth Mellins, Kira Astakhova*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Multiple drugs have been proposed for reducing harsh symptoms of human rheumatic diseases. However, a targeted therapy with mild to no side-effects is still missing. In this study, we have prepared and tested a series of therapeutic nanoparticles for specific targeting of human neutrophils associated with rheumatoid arthritis. In doing this, a series of citrullinated peptide epitopes derived from human proteins fibrinogen, vimentin and histone 3, were screened with regard to specific recognition of neutrophils. The most potent epitope proved to be a mutated fragment of an alpha chain in human fibrinogen. Next, a straightforward synthetic strategy was developed for nanoparticles decorated with this citrullinated peptide epitope and an antisense oligonucleotide targeting disease associated microRNA miR-125b-5p. Our study shows that the nanoparticles specifically recognize neutrophils and knock down miR-125b-5p, with no apparent toxicity to human cells. In contrast to organic dendrimers, chitosan-hyaluronic acid formulations do not activate human innate immune response. Our data proves that the strategy we report herein is effective in developing peptide epitopes for decorating delivery vesicles bearing biological drugs, targeted to a specific cell type.
Original languageEnglish
JournalBioconjugate Chemistry
Volume30
Issue number10
Pages (from-to)2584-2593
Number of pages10
ISSN1043-1802
DOIs
Publication statusPublished - 2019

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