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Well-Defined Bifunctional Dendrimer Bearing 54 Nitric Oxide-Releasing Moieties and 54 Ursodeoxycholic Acid Groups Presenting High Anti-Inflammatory Activity

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Author(s):
Garzon-Porras, Ana M. ; Bertuzzi, Diego L. ; Lucas, Kurt ; Ornelas, Catia
Total Authors: 4
Document type: Journal article
Source: ACS BIOMATERIALS SCIENCE & ENGINEERING; v. N/A, p. 17-pg., 2022-11-22.
Abstract

Nitric oxide (NO) and ursodeoxycholic acid (UDCA) are endogenous molecules involved in physiological processes associated with inflammation. Since inflammatory processes are present in the mechanisms of many diseases, these molecules are important for the development of new drugs. Herein, we describe the synthesis of a well-defined bifunctional dendrimer with 108 termini bearing 54 NO-releasing groups and 54 UDCA units (Dendri-(NO/UDCA)54). For comparison, a lower-generation dendrimer bearing 18 NO-releasing groups and 18 UDCA units (Dendri-(NO/UDCA)18) was also synthesized. The anti-inflamma-tory activity of these dendrimers was evaluated, showing that the bifunctional dendrimers have an inverse correlation between concentration and anti-inflammatory activity, with an effect dramatically pronounced for Dendri-(NO/UDCA)54 20, which at just 0.25 nM inhibited 76.1% of IL-8 secretion. Data suggest that nanomolar concentrations of these dendrimers aid in releasing NO in a safe and controlled way. This bifunctional dendrimer has great potential as a drug against multifactorial diseases associated with inflammatory processes. (AU)

FAPESP's process: 18/02093-0 - Development of new nanomaterials for nanomedicine applications
Grantee:Cátia Cristina Capêlo Ornelas Megiatto
Support Opportunities: Regular Research Grants
FAPESP's process: 15/04929-0 - Development of biosensors for instantaneous detection of proteins and cancer cells, for application on on-site biopsy
Grantee:Diego Luan Bertuzzi
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 21/00555-9 - Development of polymeric nanoparticles and multifunctional dendrimers for drug delivery
Grantee:Igor Dias Jurberg
Support Opportunities: Regular Research Grants