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Fluorinated PLGA-PEG-Mannose Nanoparticles for Tumor-Associated Macrophage Detection by Optical Imaging and MRI
Giorgia Zambito1,2,3, Siyuan Deng4, Joost Haeck5
1Department of Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, Netherlands.
Abstract:
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.
Insights
This study introduces a novel method using Fluorine-19 MRI to visualize tumor-associated macrophages (TAMs). This technique tracks immune cells in vivo, potentially enabling earlier cancer detection and treatment.
Area of Science:
- Biomedical Imaging
- Nanotechnology
- Immunology
Background:
- Tumor-associated macrophages (TAMs) are crucial in cancer progression and metastasis.
- The dynamic tumor microenvironment (TME) complicates understanding TAM roles.
- Visualizing TAMs in vivo is essential for cancer research and therapy.
Purpose of the Study:
- To develop and validate a method for visualizing TAMs using optical imaging and 19F MRI.
- To assess the safety and efficacy of mannose-targeted nanoparticles for TAM imaging.
- To explore the potential of 19F MRI for early cancer detection.
Main Methods:
- Development of PLGA-PEG-mannose nanoparticles (NPs) encapsulating a 19F MRI contrast agent (PFCE).
- Targeting TAMs via mannose receptors (MRC1/CD206) overexpressed on these cells.
- In vitro confirmation of NP uptake by macrophages and in vivo imaging in 4T1 xenograft mouse models.
Main Results:
- PLGA-PEG-mannose NPs demonstrated no toxicity and were effectively phagocytized by macrophages.
- In vivo 19F MRI confirmed significant NP retention at the tumor site 48 hours post-injection.
- The absence of 19F background signals ensured robust and specific imaging.
Conclusions:
- 19F MRI provides a highly specific and sensitive method for visualizing TAMs in vivo.
- This imaging approach holds promise for early cancer detection and guiding therapeutic interventions in solid tumors.
- Targeted nanoparticles offer a viable strategy for immune cell tracking in the TME.
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