Lee, Wonhwa Park, Eun Ji Kwon, Oh Kwang Kim, Hyelim Yoo, Youngbum Kim, Shin-Woo Seo, Young-Kyo Kim, In-San Na, Dong Hee Bae, Jong-Sup 2024-01-19T17:04:09Z 2024-01-19T17:04:09Z 2021-09-05 2020-07 0142-9612 https://pubs.kist.re.kr/handle/201004/118439 Sepsis is a potentially fatal complication of infections and there are currently no effective therapeutic options for severe sepsis. In this study, we revealed the secretion mechanism of transforming growth factor beta-induced protein (TGFBIp) that was recently identified as a therapeutic target for sepsis, and designed TGFBIp acetylation inhibitory peptide (TAIP) that suppresses acetylation of lysine 676 in TGFBIp. To improve bioavailability and biodegradation of the peptide, TAIP was conjugated to polyamidoamine (PAMAM) dendrimers. Additionally, the cell-penetrating peptide (CPP) was conjugated to the TAIP-modified PAMAM dendrimers for the intracellular delivery of TGFBIp. The resulting nanostructures, decorated with TAIP and CPP via poly(ethylene glycol) linkage, improved the mortality and organ damage in the septic mouse model and suppressed lipopolysaccharide-activated severe vascular inflammatory responses in endothelial cells. Thus, the dendrimer-based nanostructures for delivery of TAIP using CPP show great promise in practical applications in sepsis therapy. English ELSEVIER SCI LTD ORGAN FAILURE PATHOPHYSIOLOGY DYSFUNCTION DELIVERY PROGRESS Dual peptide-dendrimer conjugate inhibits acetylation of transforming growth factor beta-induced protein and improves survival in sepsis Article 10.1016/j.biomaterials.2020.120000 1 BIOMATERIALS, v.246 BIOMATERIALS 246 scie scopus 000526971200005 2-s2.0-85082714271 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article ORGAN FAILURE PATHOPHYSIOLOGY DYSFUNCTION DELIVERY PROGRESS Sepsis Transforming growth factor beta-induced protein Acetylation inhibitory peptide Dendrimer Nanodrug delivery