Use of carbosilane dendrimer to switch macrophage polarization for the acquisition of antitumor functions.

Abstract

Tumor microenvironment favors the escape from immunosurveillance by promoting immunosuppression and blunting pro-inflammatory responses. Since most tumor-associated macrophages (TAM) exhibit an M2-like tumor cell growth promoting polarization, we have studied the role of 2G-03NN24 carbosilane dendrimer in M2 macrophage polarization to evaluate the potential application of dendrimers in tumor immunotherapy. We found that the 2G-03NN24 dendrimer decreases LPS-induced IL-10 production from in vitro generated monocyte-derived M2 macrophages, and also switches their gene expression profile towards the acquisition of M1 polarization markers (INHBA, SERPINE1, FLT1, EGLN3 and ALDH1A2) and the loss of M2 polarization-associated markers (EMR1, IGF1, FOLR2 and SLC40A1). Furthermore, 2G-03NN24 dendrimer decreases STAT3 activation. Our results indicate that the 2G-03NN24 dendrimer can be a useful tool for antitumor therapy by virtue of its potential ability to limit the M2-like polarization of TAM.

• Authors: Ana J Perisé-Barrios, Rafael Gómez, Angel L Corbí, Javier de la Mata, Angeles Domínguez-Soto, María A Muñoz-Fernandez
• Journal: Nanoscale (Nanoscale) Vol. 7 Issue 9 Pg. 3857-66 (Mar 07 2015) ISSN: 2040-3372 [Electronic] England
• PMID: 25254497 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2G-03NN24
• Biomarkers
• Dendrimers
• Lipopolysaccharides
• Organosilicon Compounds
• STAT3 Transcription Factor
• Silanes
• carbosilane
• Interleukin-10

Topics

• Biomarkers (metabolism)
• Cell Polarity (drug effects)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Dendrimers (chemistry, pharmacology)
• Humans
• Immunotherapy
• Interleukin-10 (metabolism)
• K562 Cells
• Lipopolysaccharides (toxicity)
• Macrophages (cytology, drug effects, metabolism)
• Monocytes (cytology)
• Neoplasms (immunology, therapy)
• Organosilicon Compounds (chemistry, pharmacology)
• Phagocytosis (drug effects)
• Phosphorylation (drug effects)
• STAT3 Transcription Factor (metabolism)
• Silanes (chemistry)