Targeted Imaging of CD206 Expressing Tumor-Associated
M2-like Macrophages Using Mannose-Conjugated Antibiofouling Magnetic
Iron Oxide Nanoparticles
Posted on 2020-06-25 - 21:04
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 (T2)
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.
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Li, Yuancheng; Wu, Hui; Ji, Bing; Qian, Weiping; Xia, Siyuan; Wang, Liya; et al. (2020). Targeted Imaging of CD206 Expressing Tumor-Associated
M2-like Macrophages Using Mannose-Conjugated Antibiofouling Magnetic
Iron Oxide Nanoparticles. ACS Publications. Collection. https://doi.org/10.1021/acsabm.0c00368