Computational Histopathological Analysis of Nanoparticle Distribution in Breast Cancer Models

While many current nanoparticle studies focus on the macroscopic distribution of nanoparticles (e.g. pharmacokinetics applications), this study investigates the microscopic distribution of iron based nanoparticles within tumors through a combined histological and computational approach. Using breast cancer as a model (due to its wide variety of cell lines and well characterized animal models), we evaluated the distribution of antibody‐conjugated nanoparticles to identify and characterize their distribution patterns in xenografts with varying amounts of target protein expression.Five breast cancer cell lines (MDA‐MB‐231, MCF7/NEO, MCF7/HER, BT474, and HCC1954) with varying expression of HER2, were grown in Nude and NOD Scid Gamma (NSG) mice. When the tumor volume reached 150mm^3, five animals were assigned to one of three groups to receive intravenous injections of PBS, bio‐ionized ferrite (BNF)‐Plain or BNF‐HER nanoparticles (5mg/animal). 24 hours later, tumors were harvested and bisected. One half was fixed in 10% formalin, cross‐sectioned for histological Prussian blue analysis, and digitized. ImageJ was employed to visualize and characterize nanoparticle distribution patterns in the Prussian blue stained tumor cross‐sections from the five xenograft models referenced above. The tumor boundary was defined by a user‐drawn region of interest (ROI) and then divided into bands of equal areas. Each quantile was analyzed for pixel density and other spatial distribution statistics.We observed little evidence of BNF‐Plain uptake, but BNF‐HER was internalized about 3 times higher in all tumors, regardless of their HER2 status. For all animals that received BNF‐HER particles, each xenograft model showed marked differences in nanoparticle uptake and distribution. Between the different xenografts, HCC1954 showed the highest accumulation of nanoparticles, followed by BT474, MCF7/HER, MCF/NEO, and MDA‐MB‐231. Certain xenograft models also displayed differences in the heterogeneity of nanoparticle dispersion: nanoparticles in BT474 were spread across the tumor, while nanoparticles in HCC1954 tumors were tightly clustered at the tumor periphery. Despite the differences in uptake and heterogeneity, the highest concentration of nanoparticles was found closer to the tumor edge than the tumor center across all xenografts.Support or Funding InformationNIH, The Jayne Koskinas Ted Giovanis Foundation for Health and PolicyThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.