Nanotheranostics 2021; 5(1):36-56. doi:10.7150/ntno.50185

Research Paper

Macrophage imaging and subset analysis using single-cell RNA sequencing

Sean Arlauckas1, Nuri Oh1, Ran Li1,2, Ralph Weissleder1,2,3, Miles A. Miller1,2✉

1. Center for Systems Biology, Massachusetts General Hospital Research Institute, Boston, MA 02114, USA
2. Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02115, USA
3. Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA

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Arlauckas S, Oh N, Li R, Weissleder R, Miller MA. Macrophage imaging and subset analysis using single-cell RNA sequencing. Nanotheranostics 2021; 5(1):36-56. doi:10.7150/ntno.50185. Available from

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Macrophages have been associated with drug response and resistance in diverse settings, thus raising the possibility of using macrophage imaging as a companion diagnostic to inform personalized patient treatment strategies. Nanoparticle-based contrast agents are especially promising because they efficiently deliver fluorescent, magnetic, and/or radionuclide labels by leveraging the intrinsic capacity of macrophages to accumulate nanomaterials in their role as professional phagocytes. Unfortunately, current clinical imaging modalities are limited in their ability to quantify broad molecular programs that may explain (a) which particular cell subsets a given imaging agent is actually labeling, and (b) what mechanistic role those cells play in promoting drug response or resistance. Highly multiplexed single-cell approaches including single-cell RNA sequencing (scRNAseq) have emerged as resources to help answer these questions. In this review, we query recently published scRNAseq datasets to support companion macrophage imaging, with particular focus on using dextran-based nanoparticles to predict the action of anti-cancer nanotherapies and monoclonal antibodies.