Authors
|
Jatczak-Pawlik, I. ; Gorzkiewicz, M. ; Studzian, M. ; Zinke, R. ; Appelhans, D. ; Klajnert-Maculewicz, B. ; Pulaski, L.
|
Title
|
Nanoparticles for directed immunomodulation: mannose-functionalized glycodendrimers induce interleukin-8 in myeloid cell lines
|
Date
|
14.12.2021
|
Number
|
59863
|
Abstract
|
New therapeutic strategies for personalized medicine need to involve innovative pharmaceutical tools, for example, modular nanoparticles designed for direct immunomodulatory properties. We synthesized mannose-functionalized poly(propyleneimine) glycodendrimers with a novel architecture, where freely accessible mannose moieties are presented on poly(ethylene glycol)-based linkers embedded within an open-shell maltose coating. This design enhanced glycodendrimer bioactivity and led to complex functional effects in myeloid cells, with specific induction of interleukin-8 expression by mannose glycodendrimers detected in HL-60 and THP-1 cells. We concentrated on explaining the molecular mechanism of this phenomenon, which turned out to be different in both investigated cell lines: in HL-60 cells, transcriptional activation via AP-1 binding to the promoter predominated, while in THP-1 cells (which initially expressed less IL-8), induction was mediated mainly by mRNA stabilization. The success of directed immunomodulation, with synthetic design guided by assumptions about mannose-modified dendrimers as exogenous regulators of pro-inflammatory chemokine levels, opens new possibilities for designing bioactive nanoparticles.
|
Publisher
|
Biomacromolecules
|
Wikidata
|
|
Citation
|
Biomacromolecules 22 (2021) 3396-3407
|
DOI
|
https://doi.org/10.1021/ACS.BIOMAC.1C00476
|
Tags
|
|