PMID- 33048944
OWN - NLM
STAT- MEDLINE
DCOM- 20201204
LR  - 20240329
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 15
IP  - 10
DP  - 2020
TI  - Mannose receptor 1 expression does not determine the uptake of high-density 
      mannose dendrimers by activated macrophages populations.
PG  - e0240455
LID - 10.1371/journal.pone.0240455 [doi]
LID - e0240455
AB  - 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 99mTc-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 IFNgamma and LPS that express lower levels of MRC1 than for macrophages treated by 
      IL-4 that express high levels of MRC1. Furthermore, the intracellular 
      99mTc-HYNIC-dendrimer-mannose-Cy7 uptake in BMDMs was not inhibited in the 
      presence of free mannose or glucose. This result suggests that 
      99mTc-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.
FAU - Kovacs, Luciana
AU  - Kovacs L
AUID- ORCID: 0000-0002-3139-7528
AD  - Centro de Investigacao Translacional em Oncologia, Instituto do Cancer do Estado 
      de Sao Paulo, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Sao 
      Paulo, Brazil.
FAU - Cabral, Pablo
AU  - Cabral P
AD  - Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de 
      Ciencias Universidad de la Republica, Montevideo, Uruguay.
FAU - Chammas, Roger
AU  - Chammas R
AD  - Centro de Investigacao Translacional em Oncologia, Instituto do Cancer do Estado 
      de Sao Paulo, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Sao 
      Paulo, Brazil.
AD  - Departamento de Radiologia e Oncologia da Faculdade de Medicina da Universidade 
      de Sao Paulo, Sao Paulo, Sao Paulo, Brazil.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201013
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Benzothiazoles)
RN  - 0 (Carbocyanines)
RN  - 0 (Dendrimers)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (MRC1 protein, mouse)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Organotechnetium Compounds)
RN  - 0 (PAMAM Starburst)
RN  - 0 (Radiopharmaceuticals)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (hydrazinonictinamide)
RN  - 207137-56-2 (Interleukin-4)
RN  - 25X51I8RD4 (Niacinamide)
RN  - 57282-58-3 (cyanine dye 7)
RN  - PHA4727WTP (Mannose)
SB  - IM
MH  - Animals
MH  - Benzothiazoles/*chemistry
MH  - Carbocyanines/*chemistry
MH  - Dendrimers/*chemistry
MH  - Interleukin-4/pharmacology
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages/cytology/drug effects/*metabolism
MH  - Male
MH  - Mannose/*chemistry
MH  - Membrane Glycoproteins/genetics/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Niacinamide/*analogs & derivatives/chemistry
MH  - Organotechnetium Compounds/*chemistry
MH  - Radiopharmaceuticals/*metabolism
MH  - Receptors, Immunologic/genetics/metabolism
PMC - PMC7553290
COIS- We have a conflict of interest to disclose, one of the authors, Roger Chammas is 
      an academic editor at PLOS ONE. This does not alter our adherence to PLOS ONE 
      policies on sharing data and materials.
EDAT- 2020/10/14 06:00
MHDA- 2020/12/15 06:00
PMCR- 2020/10/13
CRDT- 2020/10/13 17:11
PHST- 2020/05/15 00:00 [received]
PHST- 2020/09/25 00:00 [accepted]
PHST- 2020/10/13 17:11 [entrez]
PHST- 2020/10/14 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2020/10/13 00:00 [pmc-release]
AID - PONE-D-20-14513 [pii]
AID - 10.1371/journal.pone.0240455 [doi]
PST - epublish
SO  - PLoS One. 2020 Oct 13;15(10):e0240455. doi: 10.1371/journal.pone.0240455. 
      eCollection 2020.