Fluorinated PLGA-PEG-Mannose Nanoparticles for Tumor-Associated Macrophage Detection by Optical Imaging and MRI

Frontiers in Medicine

Joost Haeck¹  Uwe Himmelreich²  Laura Mezzanotte³  Clemens Löwik³  Giorgia Zambito⁴  Natasa Gaspar⁵  Roberta Censi⁶  Piera Di Martino⁶  Siyuan Deng⁶ 

[1] Applied Molecular Imaging Facility of Erasmus MC (AMIE) Core Facility, Erasmus Medical Center, Rotterdam, Netherlands;Biomedical MR Unit, Molecular Small Animal Imaging Center (MoSAIC), University of Leuven (KU Leuven), Leuven, Belgium;Department of Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, Netherlands;Department of Molecular Genetics, Erasmus Medical Center, Rotterdam, Netherlands;Department of Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, Netherlands;Department of Molecular Genetics, Erasmus Medical Center, Rotterdam, Netherlands;Medres Medical Research GmBH, Cologne, Germany;Department of Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, Netherlands;Department of Molecular Genetics, Erasmus Medical Center, Rotterdam, Netherlands;Percuros B.V., Enschede, Netherlands;School of Pharmacy, University of Camerino, Camerino, Italy;

关键词: cell tracking;    perfluorocarbon;    tumor-associated macrophage;    contrast agent;    F;    magnetic resonance imaging;    breast cancer;   

DOI  :  10.3389/fmed.2021.712367

来源: Frontiers

【 摘 要 】

Tumor-associated macrophages (TAMs) promote cancer growth and metastasis, but their role in tumor development needs to be fully understood due to the dynamic changes of tumor microenvironment (TME). Here, we report an approach to visualize TAMs by optical imaging and by Fluorine-19 (19F) magnetic resonance imaging (MRI) that is largely applied to track immune cells in vivo. TAMs are targeted with PLGA-PEG-mannose nanoparticles (NPs) encapsulating perfluoro-15-crown-5-ether (PFCE) as MRI contrast agent. These particles are preferentially recognized and phagocytized by TAMs that overexpress the mannose receptor (MRC1/CD206). The PLGA-PEG-mannose NPs are not toxic and they were up-taken by macrophages as confirmed by in vitro confocal microscopy. At 48 h after intravenous injection of PLGA-PEG-mannose NPs, 4T1 xenograft mice were imaged and fluorine-19 nuclear magnetic resonance confirmed nanoparticle retention at the tumor site. Because of the lack of 19F background in the body, observed 19F signals are robust and exhibit an excellent degree of specificity. In vivo imaging of TAMs in the TME by 19F MRI opens the possibility for detection of cancer at earlier stage and for prompt therapeutic interventions in solid tumors.

【 授权许可】

CC BY