(6gt) Iron Oxide Nanoparticles Inhibit Metastasis and Tumor Growth in Lung

My research goals are directed toward developing Clinical Translational nanoscale technologies with particular emphasis on developing nanoscale biomaterials and immunoengineering systems for cancer immunotherapy, drug delivery and molecular/cellular imaging. My goal is to link the fields of nanotechnology, immunotherapy, cellular biology, and medical imaging towards more efficient and accurate diagnosis, personalized therapies and ultimately improving treatment outcomes and patient quality of life.

Teaching Interests:

My teaching interests lie in the interface of nanotechnology, cancer immunotherapy, cell biology, and medical imaging.

Iron oxide nanoparticles inhibit metastasis and tumor growth in lung

Saeid Zanganeh¹, Morteza Mahmoudi²

¹Sloan Kettering Institute for Cancer Research, New York, New York 10065, USA

²Center for Nanomedicine, Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, United States

Introduction:

We recently revealed a hidden therapeutic effect of the iron oxide nanoparticles (ferumoxytol) on the breast cancer tumors. Here, we show the immunotherapeutic effect of these nanoparticles on the growth of metastatic tumors in lung. We hypothesized that ferumoxytol nanoparticles inhibited cancer metastases by inducing a pro-inflammatory immune response with M1 macrophage polarization. In vitro, Macrophages exposed to ferumoxytol displayed increased mRNA/cytokines associated with pro-inflammatory Th1-type responses. In vivo, intravenous ferumoxytol treatment before intravenous tumour cell challenge prevented development of lung metastasis. Fluorescence-activated cell sorting (FACS) and histopathology studies showed that the observed tumour growth inhibition was accompanied by increased presence of pro-inflammatory M1 macrophages in the tumour tissues. Our results suggest that ferumoxytol could be applied ‘off label’ to protect the lung from metastatic seeds and potentiate macrophage-modulating cancer immunotherapies.

Materials and Methods: Most experiments were performed with the ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle compound Ferumoxytol (Feraheme®, AMAG Pharmaceuticals Inc., Cambridge, MA, USA). The chemotactic effects were studied using Transwell assays with MMTV-PyMT cancer cells and bone marrow derived macrophages. Real-time PCR, ELISA assays, and ROS measurements were performed in vitro. lung tumors were studied using FACS and followed by histopathology.

Results and Discussion: Through the in vitro and in vivo experiments, we revealed the following: (1) Low dose ferumoxytol was not cytotoxic. (2) Ferumoxytol increased macrophage migration. (3) Ferumoxytol causes in vivo M1 macrophage polarization. (4) Systemic delivery of ferumoxytol inhibits lung metastases. (5) Pre-treatment with ferumoxytol inhibits development of lung metastases. (6) Ferumoxytol alters macrophage polarization in lung metastasis in vivo. (8) α-CSF1 monoclonal antibody treatment inhibits ferumoxytol effects on tumor growth.

Conclusions: We hypothesized that ferumoxytol nanoparticles inhibited cancer growth by inducing a pro-inflammatory immune response with M1 macrophage polarization. The intrinsic impact of nanoparticles on macrophage physiology is not well understood. To our knowledge, no one has investigated intrinsic effects of iron oxide nanoparticles on macrophage physiology in cancer. The results have broad implications for diagnostic and therapeutic nanoparticle applications.