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Cell-penetrating peptides released from thermosensitive nanoparticles suppress pro-inflammatory cytokine response by specifically targeting inflamed cartilage explants

Nanomedicine. 2013 Apr;9(3):419-427. doi: 10.1016/j.nano.2012.09.003. Epub 2012 Oct 3.

Abstract

Cell-penetrating anti-inflammatory peptide KAFAKLAARLYRKALARQLGVAA (KAFAK) has the ability to suppress pro-inflammatory cytokines TNF-α and IL-6 when released from degradable and non-degradable poly(NIPAm-AMPS) nanoparticles. In vitro human macrophage model with THP1 human monocytes and ex vivo bovine knee cartilage tissue both showed a dose-dependent suppression of pro-inflammatory cytokines when treated with KAFAK-loaded poly(NIPAm-AMPS) nanoparticles. When bovine knee cartilage explants were treated with KAFAK-loaded poly(NIPAm-AMPS) nanoparticles, rapid and highly selective targeting of only damaged tissue occurred. This study has demonstrated selective targeting and therapeutic efficacy of KAFAK when released from both degradable and non-degradable poly(NIPAm-AMPS) nanoparticles in in vitro and ex vivo models. As a result, poly(NIPAm-AMPS) nanoparticles loaded with KAFAK could be a very effective tool to treat osteoarthritis.

From the clinical editor: Inflammatory arthritis remains a major medical problem with substantial socio-economic impact. Anti-inflammatory KAFAK peptide when released from degradable and non-degradable poly(NIPAm-AMPS) nanoparticles has the ability to penetrate cells and suppress pro-inflammatory cytokines, resulting in rapid and highly selective targeting of only damaged tissue in bovine knee cartilage explants. This approach may provide a very effective future tool in addressing osteoarthritis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acrylic Resins / chemistry
  • Amino Acid Sequence
  • Animals
  • Cartilage / drug effects
  • Cartilage / metabolism
  • Cartilage / pathology*
  • Cattle
  • Cell Line
  • Cell-Penetrating Peptides / chemistry
  • Cell-Penetrating Peptides / pharmacology*
  • Cytokines / metabolism*
  • Humans
  • Inflammation / pathology*
  • Inflammation Mediators / metabolism*
  • Interleukin-6 / biosynthesis
  • Macrophages / metabolism
  • Molecular Sequence Data
  • Nanoparticles / chemistry*
  • Polymers / chemistry
  • Sulfonic Acids / chemistry
  • Temperature*
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Acrylic Resins
  • Cell-Penetrating Peptides
  • Cytokines
  • Inflammation Mediators
  • Interleukin-6
  • Polymers
  • Sulfonic Acids
  • Tumor Necrosis Factor-alpha
  • poly-N-isopropylacrylamide
  • poly(2-acrylamido-2-methyl-1-propanesulfonic acid)