title: Cell-penetrating peptides released from thermosensitive nanoparticles suppress pro-inflammatory cytokine response by specifically targeting inflamed cartilage explants.
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.
  
  
  BACKGROUND
  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.
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, 206 S. Martin Jischke Drive, West Lafayette Indiana, 47907.
authors.forename: Rush L
authors.initials: RL
authors.lastname: Bartlett
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, 206 S. Martin Jischke Drive, West Lafayette Indiana, 47907.
authors.forename: Shaili
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, 206 S. Martin Jischke Drive, West Lafayette Indiana, 47907.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Panitch
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002417:Cattle; D002460:Cell Line; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D013451:Sulfonic Acids / Q000737:chemistry; D013696:Temperature; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000180:Acrylic Resins; D057846:Cell-Penetrating Peptides; D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D011108:Polymers; D013451:Sulfonic Acids; D014409:Tumor Necrosis Factor-alpha; C052970:poly-N-isopropylacrylamide; C077118:poly(2-acrylamido-2-methyl-1-propanesulfonic acid)