A dynamic magnetic shift method to increase nanoparticle concentration in cancer metastases: a feasibility study using simulations on autopsy specimens

Abstract

Alek Nacev1, Skye H Kim2, Jaime Rodriguez-Canales2, Michael A Tangrea2, Benjamin Shapiro1, Michael R Emmert-Buck21Fischell Department of Bioengineering, University of Maryland, College Park, MD; 2Pathogenetics Unit, Laboratory of Pathology, Center for Cancer Research National Cancer Institute, National Institutes of Health, Bethesda, MD, USAAbstract: A nanoparticle delivery system termed dynamic magnetic shift (DMS) has the potential to more effectively treat metastatic cancer by equilibrating therapeutic magnetic nanoparticles throughout tumors. To evaluate the feasibility of DMS, histological liver sections from autopsy cases of women who died from breast neoplasms were studied to measure vessel number, size, and spatial distribution in both metastatic tumors and normal tissue. Consistent with prior studies, normal tissue had a higher vascular density with a vessel-to-nuclei ratio of 0.48 ± 0.14 (n = 1000), whereas tumor tissue had a ratio of 0.13 ± 0.07 (n = 1000). For tumors, distances from cells to their nearest blood vessel were larger (average 43.8 µm, maximum 287 µm, n ≈ 5500) than normal cells (average 5.3 µm, maximum 67.8 µm, n ≈ 5500), implying that systemically delivered nanoparticles diffusing from vessels into surrounding tissue would preferentially dose healthy instead of cancerous cells. Numerical simulations of magnetically driven particle transport based on the autopsy data indicate that DMS would correct the problem by increasing nanoparticle levels in hypovascular regions of metastases to that of normal tissue, elevating the time-averaged concentration delivered to the tumor for magnetic actuation versus diffusion alone by 1.86-fold, and increasing the maximum concentration over time by 1.89-fold. Thus, DMS may prove useful in facilitating therapeutic nanoparticles to reach poorly vascularized regions of metastatic tumors that are not accessed by diffusion alone.Keywords: cancer, metastases, vasculature, drug delivery, magnetic, nanoparticles