The use of magnetic nanoparticle therapy has promise as a cell specific/high therapeutic ratio, low-toxicity cancer therapy. The most attractive feature of mNP-AMF cancer therapy is the ability to deliver mNP to individual cancer cells via peptide targeting and to selectively kill such cells by exciting the mNPs with a noninvasive/ safe alternating magnetic field (AMF). Project 3 will perform a variety of fundamental studies required to support planned clinical trials for breast cancer using mNP-AMF therapy at Dartmouth. Our preliminary data demonstrate the ability to completely control murine breast tumors with mNP-AMF therapy.
Aim 1 investigates performance impact of a variety of mNP variables including, size, delivery route, and antibody targeting, both in vitro in breast cancer cell lines and in vivo with the same cells in syngeneic or xenogeneic grafts in mice.
Aim 2 exploits our preliminary data suggesting a reduction of interstitial tumor pressure improves nanoparticle delivery and biodistribution in tumors and investigates the in vivo impact of such reduction. mNP-AMF can among other potential effects generate local hyperthermia and mild hyperthermia is well documented in vitro, in animals and patients to significantly increase the effectiveness of conventional cancer treatment modalities such as radiation and chemotherapy.
Aim 3 investigates the synergy between mNP-AMF and radiation or chemotherapy.
Aim 4 is designed to directly support the planned clinical trials of mNP-AMF therapy for breast cancer at Dartmouth. Our preliminary experiments have allowed us to define appropriate parameters for mNP-AMF treatment for mice. While extremely useful, this information will not translate directly to human patients.
Aim 4 will use human breast and tumor phantoms and an in vivo porcine breast model (we have the appropriate generator and coils) to determine optimal mNP and AMF delivery techniques for the human breast cancer patient. Project 3 will interact with all other projects and cores. The nanoparticle core will supply particles, as will project 1. Projects 1 and 2 will use the models generated by project 3. Project 4 will use the AMF equipment housed in project 3 and interact intellectually with project 3 since each both are using mNP-AMF for therapy. Pathology, Toxicology and Biodistribution core will analyze mNP biodistribution and the Bioinformatics, Statistics and Data Analysis core will perform data analysis and support experimental design.

Public Health Relevance

Project 3 is focused on the preclinical studies needed to support the use of mNP-AMF technology as a therapy against breast cancer. These breast cancer model studies include how to optimize particle characteristics and delivery, how best to combine mNP-AMF with chemotherapy and radiation and the crucial studies in breast phantoms and large animals that will for the first time investigate parameters for using mNPP-AMF in humans.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Dartmouth College
United States
Zip Code
Hoopes, P Jack; Wagner, Robert J; Duval, Kayla et al. (2018) Treatment of Canine Oral Melanoma with Nanotechnology-Based Immunotherapy and Radiation. Mol Pharm 15:3717-3722
Pearce, John A; Petryk, Alicia A; Hoopes, P Jack (2017) Numerical Model Study of In Vivo Magnetic Nanoparticle Tumor Heating. IEEE Trans Biomed Eng 64:2813-2823
Fang, Yongliang; Chu, Thach H; Ackerman, Margaret E et al. (2017) Going native: Direct high throughput screening of secreted full-length IgG antibodies against cell membrane proteins. MAbs 9:1253-1261
Hoopes, P Jack; Wagner, Robert J; Song, Ailin et al. (2017) The effect of hypofractionated radiation and magnetic nanoparticle hyperthermia on tumor immunogenicity and overall treatment response. Proc SPIE Int Soc Opt Eng 10066:
Hoopes, P Jack; Moodie, Karen L; Petryk, Alicia A et al. (2017) Hypo-fractionated Radiation, Magnetic Nanoparticle Hyperthermia and a Viral Immunotherapy Treatment of Spontaneous Canine Cancer. Proc SPIE Int Soc Opt Eng 10066:
Ficko, Bradley W; NDong, Christian; Giacometti, Paolo et al. (2017) A Feasibility Study of Nonlinear Spectroscopic Measurement of Magnetic Nanoparticles Targeted to Cancer Cells. IEEE Trans Biomed Eng 64:972-979
Hoopes, P Jack; Mazur, Courtney M; Osterberg, Bjorn et al. (2017) Effect of intra-tumoral magnetic nanoparticle hyperthermia and viral nanoparticle immunogenicity on primary and metastatic cancer. Proc SPIE Int Soc Opt Eng 10066:
Kekalo, Katsiaryna; Shubitidze, Fridon; Meyers, Robert et al. (2016) Magnetic Heating of Fe-Co Ferrites: Experiments and Modeling. Nano Life 6:
Allegrezza, Michael J; Rutkowski, Melanie R; Stephen, Tom L et al. (2016) IL15 Agonists Overcome the Immunosuppressive Effects of MEK Inhibitors. Cancer Res 76:2561-72
Tesone, Amelia J; Rutkowski, Melanie R; Brencicova, Eva et al. (2016) Satb1 Overexpression Drives Tumor-Promoting Activities in Cancer-Associated Dendritic Cells. Cell Rep 14:1774-1786

Showing the most recent 10 out of 112 publications