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. From the Clinical EditorInflammatory 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.