Citrullinated Peptide Epitope Targets Therapeutic Nanoparticles to Human Neutrophils
Khatri S., Hansen J., Mendes A. C., Chronakis I. S., Hung S. -., Mellins E. D., Astakhova K.
Bioconjugate Chemistry
Vol.30, Issue10, P. 2584-2593
Опубликовано: 2019
Тип ресурса: Статья
DOI:10.1021/acs.bioconjchem.9b00518
Аннотация:
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
Ключевые слова:
epitope; fibrinogen; histone H3; microRNA 125b; microRNA 125b 5p; nanoparticle; peptide; unclassified drug; vimentin; epitope; nanoparticle; peptide; alpha chain; Article; citrullination; controlled study; gene knockdown; human; human cell; innate immunity; molecular recognition; neutrophil; amino acid sequence; chemistry; drug effect; metabolism; neutrophil; Amino Acid Sequence; Citrullination; Epitopes; Humans; Nanoparticles; Neutrophils; Peptides
Язык текста: Английский
ISSN: 1520-4812
Khatri S.
Hansen J.
Mendes A. C.
Chronakis I. S.
Hung S. -. S.-C.
Mellins E. D.
Astakhova K.
Хатри С.
Хансен Й.
Мендес А. C.
Чронакис И. С.
Хунг С. -. С.-C.
Меллинс Е. Д.
Астахова К.
Citrullinated Peptide Epitope Targets Therapeutic Nanoparticles to Human Neutrophils
Текст визуальный непосредственный
Bioconjugate Chemistry
American Chemical Society
Vol.30, Issue10 P. 2584-2593
2019
Статья
epitope fibrinogen histone H3 microRNA 125b microRNA 125b 5p nanoparticle peptide unclassified drug vimentin epitope nanoparticle peptide alpha chain Article citrullination controlled study gene knockdown human human cell innate immunity molecular recognition neutrophil amino acid sequence chemistry drug effect metabolism neutrophil Amino Acid Sequence Citrullination Epitopes Humans Nanoparticles Neutrophils Peptides
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