1. Nanoparticles for Directed Immunomodulation: Mannose-Functionalized Glycodendrimers Induce Interleukin-8 in Myeloid Cell Lines
- Author
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Robin Zinke, Barbara Klajnert-Maculewicz, Łukasz Pułaski, Maciej Studzian, Michał Gorzkiewicz, Izabela Jatczak-Pawlik, and Dietmar Appelhans
- Subjects
Dendrimers ,Chemokine ,Polymers and Plastics ,Mannose ,Bioengineering ,Article ,Cell Line ,Propyleneimine ,Immunomodulation ,Biomaterials ,chemistry.chemical_compound ,Dendrimer ,Materials Chemistry ,Humans ,Myeloid Cells ,Interleukin 8 ,biology ,Interleukin-8 ,MRNA stabilization ,Cell biology ,Pharmaceutical Preparations ,chemistry ,Cell culture ,biology.protein ,Nanoparticles ,Ethylene glycol - 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.
- Published
- 2021
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