Anti-inflammatory activity of polyamide dendrimers bearing bile acid termini synthesized via SPAAC

Autor(es)

Garzon-Porras, Ana M. ^{[1, 2]} ; Bertuzzi, Diego L. ^[1] ; Lucas, Kurt ^[2] ; Ornelas, Catia ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Inst Chem, UNICAMP, BR-13083970 Campinas, SP - Brazil

^[2] Max Planck Inst Chem, Hahn Meitner Weg 1, D-55128 Mainz - Germany

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF NANOPARTICLE RESEARCH; v. 21, n. 11 NOV 2019.
• Citações Web of Science: 0

Resumo

Inflammation is a general pathomechanism associated with numerous diseases of global impact such as many cancers, metabolic disorders, and neurodegenerative and autoimmune diseases. The development of drugs that can treat chronic inflammation, in an effective way and that are well tolerated by the patients, is an active research area that pursues the treatment for hundreds of diseases. Dendrimers recently appeared as a convenient starting point for the design of anti-inflammatory drugs due to its nanosize, well-defined branched structure, multivalency, and versatility. In this work, polyamide dendrimers with 1 \& x2794; 3 connectivity were synthesized and functionalized with three types of bile acids (BAs): cholic acid (CA), ursodeoxycholic acid (UDCA), and chenodeoxycholic acid (CDCA). Functionalization was carried out through strain-promoted alkyne-azide cycloaddition (SPAAC) between an azide dendrimer and cyclooctyne derivatives of bile acids. The cell viability and the anti-inflammatory potential of the bile acid dendrimers were evaluated in vitro and compared with those of the pure BAs. The bile acid dendrimers and pure BAs did not show significant cytotoxicity at the concentrations tested (0.78-5.00 x 10(4) nM) against THP-1 cells. Chenodeoxycholic acid (CDCA) and the corresponding dendrimer dendri-(CDCA)(18) (polyamide dendrimer bearing 18 CDCA moieties) presented the highest anti-inflammatory activity, showing LPS-induced IL-8 release inhibition of 45.3% at 0.78 nM CDCA and 35.5% at 0.43 nM dendri-(CDCA)(18). (AU)

• Processo FAPESP: 18/02093-0 - Desenvolvimento de novos nanomateriais para aplicações em nanomedicina
• Beneficiário: Cátia Cristina Capêlo Ornelas Megiatto
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/04929-0 - Desenvolvimento de biosensores para detecção instantânea de proteínas e de células cancerígenas, para aplicação em biópsias on-site
• Beneficiário: Diego Luan Bertuzzi
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto