Researcher: Seoyoon Song
Colaborators: Melissa Cadena, Myeongsoo Kim
Background
Reinforcing antitumor functions of macrophages, phagocytosis of cancer cells and secretion of inflammatory cytokines, can be a potent approach to treat solid tumors. Several strategies including CAR-macrophages have been reported and have shown promise in preclinical models. However, these approaches lack mechanisms for monitoring transferred macrophages and assessing their therapeutic efficacy against tumors, limiting the ability to implement longitudinal therapeutic interventions throughout the treatment.
Integrating imaging and contrast agents offers a possibility for real-time and non-invasive tracking of macrophages within the tumor microenvironment. Specifically, labeling macrophages with imaging contrast agents allows for longitudinal visualization of their migration, infiltration, and persistence in tumors, which could serve as an indicator of therapeutic response. Photoacoustic (PA) imaging is a technique that combines ultrasound and optical imaging by leveraging the light-to-sound conversion under laser irradiation of optical absorbers with high-intensity nanosecond laser pulses. PA imaging offers a powerful tool for real-time and noninvasive tracking of adoptively transferred cells.
Here, we propose a macrophage engineering strategy for PA image-guided cancer immunotherapy. A nanoparticle formulation with both PA contrast and immunomodulatory effects is synthesized. Macrophages labeled with the formulated nanoparticles demonstrated strong antitumoral phenotypes and allowed longitudinal PA imaging. Our work provides perspectives on engineering macrophages for image-guided cancer immunotherapy.
Results
Photostable HBGNCs with high optical absorption efficiency, ~90% in the near-infrared I (NIR I) region, were synthesized. The enhanced optical absorption was attributed to the hyper-branched structure. Due to the enhanced optical responses at NIR I region, the HBGNCs produced robust photoacoustic (PA) responses at corresponding wavelengths, offering high sensitivity in PA imaging.
When macrophages were labeled with HBGNCs, the size and the granularity of the cells increased as the particles were internalized. The labeling did not affect the viability of the cells. HBGNC-labeled macrophages embedded in tissue-mimicking phantoms yielded high PA signal.
The migration ability of the labeled macrophages was evaluated. Compared to IFNg-primed macrophages that are known to migrate at a high rate, macrophages labeled with either HBGNCs or HBGNC-Gs displayed a superior migration ability.
The phenotype of macrophages became more strongly anti-tumoral when labeled with IFNg-conjugated HBGNCs (HBGNC-Gs) compared to HBGNC and IFNg alone. This was supported by the increased expression of costimulatory receptors CD80 and CD86, MHCII, and the decreased expression of pro-tumoral marker CD206.
Conclusion
In the current study, a new strategy of macrophage engineering for cancer immunotherapy was introduced. Labeling macrophages with HBGNC-Gs have enabled PA imaging of macrophages and, at the same time, enhanced their migration ability and antitumoral phenotype. Results suggest that HBGNC labeling approach can provide insights into developing strategies for macrophage-based cancer immunotherapy.