Dataset Information

Targeted Imaging of CD206 Expressing Tumor-Associated M2-like Macrophages Using Mannose-Conjugated Antibiofouling Magnetic Iron Oxide Nanoparticles.

ABSTRACT: Although tumor-associated macrophages (TAMs) have been shown to promote cancer progression, their roles in tumor development and resistance to therapy remain to be fully understood, mainly because of the lack of a good approach to evaluate the dynamic changes of heterogeneous macrophages in their residing microenvironment. Here, we report an approach of using antibiofouling PEG-b-AGE polymer-coated iron oxide nanoparticles (IONPs) for targeted imaging of mannose receptor (CD206)-expressing M2-like TAMs. Antibiofouling polymer coatings block non-specific phagocytosis of IONPs by different cells but enable ligand-mediated CD206⁺ M2-like macrophage targeting after surface functionalizing with mannose (Man-IONP). Costaining tissue sections of the 4T1 mouse mammary tumors using an anti-CD206 antibody and fluorescent dye (TRITC)-labeled Man-IONP showed 94.7 ± 4.5% colocalization of TRITC-Man-IONPs with the anti-CD206 antibody. At 48 h after intravenous (i.v.) injection of Man-IONPs, magnetic resonance imaging of mice bearing orthotopic 4T1 mammary tumors showed a significantly larger IONP-induced decrease of the transverse relaxation time (T ₂) in tumors with 29.4 ± 1.5 ms compared to 12.3 ± 3.6 ms in tumors that received non-targeted IONP probes (P < 0.001). Immunofluorescence-stained tumor tissue sections collected at 6, 18, and 24 h after i.v. administration of the nanoprobes revealed that Man-IONPs specifically targeted CD206⁺ M2-like macrophages in various tumor areas at all time points, while nonconjugated IONPs were absent in the tumor after 18 h. Thus, antibiofouling Man-IONPs demonstrated the capability of explicitly imaging CD206⁺ M2-like macrophages in vivo and potentials for investigating the dynamics of macrophages in the tumor microenvironment and delivering therapeutics targeting M2-like TAMs.

SUBMITTER: Li Y

PROVIDER: S-EPMC8626204 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Macrophages (MΦs) play important roles in implantation. Depletion of CD11b+ pan-MΦs in CD11b-diphtheria-toxin-receptor (DTR) mice is reported to cause implantation failure due to decreased progesterone production in the corpus luteum. However, of the M1 and M2, the type of MΦs that is important for implantation is unknown. In this study, we investigated the role of M2 MΦ in implantation using CD206-DTR mice. To deplete M2-MΦ, female CD206-DTR C57/BL6 mice were injected with DT before implantation. These M2-MΦ depleted mice (M2(-)) were naturally mated with Balb/C mice. As the control group, female C57/BL6 wild type (WT) mice injected with DT were mated with male Balb/C mice. The number of implantation sites and plasma progesterone levels at implantation were examined. Implantation-related molecule expression was determined using quantitative-PCR and immunohistochemistry of uterine tissues. The mRNA expression in the endometrial tissues of 38 patients with implantation failure was examined during the implantation window. In WT mice, CD206+M2-like MΦs accumulated in the endometrium at the implantation period, on embryonic (E) 4.5. In M2(-), the implantation number was significantly lower than that in control (p < 0.001, 7.8 ± 0.8 vs. 0.2 ± 0.4), although the plasma progesterone levels were not changed. Leukemia inhibitory factor (LIF) and CD206 mRNA expression was significantly reduced (p < 0.01), whereas the levels of TNFα were increased on E4.5 (p < 0.05). In M2(-), the number of Ki-67+ epithelial cells was higher than that in control at the pre-implantation period. Accelerated epithelial cell proliferation was confirmed by significantly upregulated uterine fibroblast growth factor (FGF)18 mRNA (P < 0.05), and strong FGF18 protein expression in M2(-) endometrial epithelial cells. Further, M2(-) showed upregulated uterine Wnt/β-catenin signals at the mRNA and protein levels. In the non-pregnant group, the proportion of M2-like MΦ to pan MΦ, CD206/CD68, was significantly reduced (p < 0.05) and the TNFα mRNA expression was significantly increased (p < 0.05) in the endometrial tissues compared to those in the pregnant group. CD206+ M2-like MΦs may be essential for embryo implantation through the regulation of endometrial proliferation via Wnt/β-catenin signaling.

Dataset Information

Targeted Imaging of CD206 Expressing Tumor-Associated M2-like Macrophages Using Mannose-Conjugated Antibiofouling Magnetic Iron Oxide Nanoparticles.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets