Mannose receptor 1 expression does not determine the uptake of high-density mannose dendrimers by activated macrophages populations

Author(s)

Kovacs, Luciana ^[1] ; Cabral, Pablo ^[2] ; Chammas, Roger ^{[1, 3]}

Affiliation

^[1] Univ Sao Paulo, Ctr Invest Translac Oncol, Inst Canc Estado Sao Paulo, Fac Med, Sao Paulo, SP - Brazil

^[2] Univ Republica, Dept Radiofarmacia, Ctr Invest Nucl, Fac Ciencias, Montevideo - Uruguay

^[3] Univ Sao Paulo, Dept Radiol & Oncol, Fac Med, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: PLoS One; v. 15, n. 10 OCT 13 2020.
• Web of Science Citations: 0

Abstract

The presence of a high number of macrophages within solid tumors is often significantly associated with poor prognosis and predict treatment failure for chemotherapy and radiotherapy. Macrophages are innate immune cells capable of performing diverse functions depending on the different signals from the microenvironment. The classically activated macrophage is commonly present during the early stages of tumor development while alternatively activated macrophages are associated with more advanced tumors. The distinction of the antitumoral macrophages from the pro-tumoral macrophages is not absolute. However, they have different cell surface markers such as mannose receptor (MRC1 or CD206) abundantly expressed by macrophages treated with interleukin-4 (IL-4). The important roles of macrophages in cancers suggest that it is important to develop novel therapies that target these cells. In the present study, we designed a probe using Polyamidoamine (PAMAM) fifth-generation (G5) dendrimers conjugated with mannose, Cyanine 7 (Cy7), and hydrazinonicotinamide (HYNIC) for target macrophages with high expression of MRC1 in the tumor. The intracellular uptake of(99m)Tc-HYNIC-dendrimer-mannose-Cy7 through the interaction with MRC1 in bone marrow-derived macrophages (BMDMs) untreated or treated with lipopolysaccharides (LPS) + interferon (IFN)gamma or IL-4 was analyzed. Our results show that high-density mannose dendrimers are preferentially bound by macrophages treated by IFN gamma and LPS that express lower levels of MRC1 than for macrophages treated by IL-4 that express high levels of MRC1. Furthermore, the intracellular(99m)Tc-HYNIC-dendrimer-mannose-Cy7 uptake in BMDMs was not inhibited in the presence of free mannose or glucose. This result suggests that(99m)Tc-HYNIC-dendrimer-mannose-Cy7 is not internalized via macrophage MRC1. Based on these findings, we concluded that MRC1 expression does not determine the uptake of high-density mannose dendrimers. (AU)

• FAPESP's process: 14/20746-0 - Development of aptamers and G5 PAMAM dendrimers for the in vivo diagnosis of M2 macrophages in tumor microenvironment
• Grantee: Luciana Kovacs dos Santos
• Support Opportunities: Scholarships in Brazil - Post-Doctoral