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.

Plasticity of antimicrobial and phagocytic programs in human macrophages

“…This is concordant with the synergy between TLR2/1L and IFN‐ γ to induce the genes encoding these antimicrobial peptides in monocytes . Hence, re‐polarization of M2 M Φ into M1 M Φ could be a powerful tool in augmenting host defense against intracellular pathogens, as well as to generate antitumor effects …”

“…14 Hence, re-polarization of M2 MΦ into M1 MΦ could be a powerful tool in augmenting host defense against intracellular pathogens, as well as to generate antitumor effects. 26,27 The conversion of M2 MΦ into M1-like MΦ was not only triggered by the addition of TLR2/1L plus IFN-c, but also by the addition of TLR2/1L plus anti-IL-10 neutralizing antibodies. Interleukin-10 has long been known to inhibit MΦ function including cytokine production 28 and antimicrobial function.…”

Adipocytes and Macrophages Interplay in the Orchestration of Tumor Microenvironment: New Implications in Cancer Progression

“…Carbosilane dendrimer 2G-03NN24 can cause polarization M2 to M1 polarization, decreasing the expression of several M2-related genes, which, in turn, increases the expression of M1 characteristics. These results were confirmed by functional assays, given the M1-oriented proinflammatory and antitumor responses ( 107 ). The mechanism involved inhibits phosphorylation of STAT3, which boosts the capacity of macrophages to promote cytotoxic response and presentation of tumor antigens ( 107 , 108 ).…”

“…These results were confirmed by functional assays, given the M1-oriented proinflammatory and antitumor responses ( 107 ). The mechanism involved inhibits phosphorylation of STAT3, which boosts the capacity of macrophages to promote cytotoxic response and presentation of tumor antigens ( 107 , 108 ). Furthermore, it has been demonstrated that a system composed of gold nanoparticles adapted with MUC-1 protein fragment was capable of promoting macrophage activation and M1 polarization, characterized by increased antigen presentation and M1-like cytokine expression ( 109 ).…”

High Preventive Effect of G2-S16 Anionic Carbosilane Dendrimer against Sexually Transmitted HSV-2 Infection

“…The potential applications of anionic dendrimers are very broad, as they could be used as antiviral and antibacterial agents [ 17 , 20 , 21 , 22 , 23 ], as carriers of chemical drugs and peptides [ 24 , 25 , 26 , 27 , 28 ], as gene silencers [ 29 ], and as potential therapeutic agents for diverse pathological conditions, including neurodegenerative diseases (such as Alzheimer´s disease) [ 30 ], cancer [ 31 , 32 , 33 ], chronic inflammatory diseases [ 34 , 35 ] and infectious diseases [ 36 ], among others.…”