Magnetic particle imaging reveals heterogeneous retention, leakage and redistribution of nanoparticles following intratumoral injection

Abstract Intratumoral (i.t.) delivery of nanoparticles (NPs) is widely used to achieve high local NP concentrations. However, the temporal fate of i.t.-injected NPs remains poorly understood. We present a quantitative approach using whole-body magnetic particle imaging (MPI) to track magnetic NPs (MNPs) following i.t. injection. Using fiducial-calibrated imaging, we quantified MNP mass over time in subcutaneous 4T1 breast tumors. Longitudinal imaging revealed progressive loss of i.t. MNP content and heterogeneous systemic redistribution across animals despite standardized delivery conditions. Ex vivo MPI confirmed off-target accumulation primarily in the liver and spleen, consistent with reticuloendothelial clearance pathways. Histological analysis demonstrated spatially heterogeneous i.t. MNP deposition, potentially associated with local vascular features and tumor microenvironmental heterogeneity that may influence i.t. MNP retention or MNP clearance from the tumor. These findings highlight the importance of quantitative longitudinal whole-body MPI for understanding the fate of MNPs for informing localized nanotherapy. Competing Interest Statement J.W.M.B. is a shareholder of SuperBranche. This arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict-of-interest policies. R.I. is an inventor listed on several nanoparticle patents. All patents are assigned to either Johns Hopkins University or Aduro Biosciences, Inc. All other authors declare they have no competing interests. Footnotes The previously uploaded file is a confidential document, as it contains information about the journal and the publisher that are considering our manuscript for publication. Here, we are uploading the manuscript without this kind of information.