Polyacrylic Acid-Modified Superparamagnetic Iron Oxide Nanoparticles Differentiate Between Hyperplastic and Metastatic Breast Cancer Lymph Nodes

Abstract

The recognition of lymph node (LN) metastasis is critical for breast cancer staging. Axillary lymph node (ALN) puncture or resection followed by biopsy, to determine whether the presence of metastasis is the diagnostic ‘gold standard’ for axillary lymph node metastasis. This procedure is an invasive procedure that triggers a series of complications. To solve this problem, we developed an ultrasmall superparamagnetic polyacrylic acid-modified iron oxide nanoparticles (PAA@IONs), which exhibit excellent physicochemical characteristics and are extremely stable in the aqueous state. They had an average hydrated particle size of 37.81±0.80 nm, average zeta potential of −38.7±3.8 mV, relaxivity R1 of 25.53±1.58 s−1mM−1, and R2 of 43.10±3.43 s−1mM−1. Animal magnetic resonance imaging (MRI) of the inflammatory hyperplasia model and tumor metastasis model of lymph nodes showed that the samples could effectively detect the metastasized tumors in lymph nodes (n =8). The inflammatory lymphadenopathy did not affect lymph node diagnosis, and this property helped overcome the challenge of current lymph node diagnosis, showing high sensitivity (100%) and specificity (83%). Body weight, hematology, coagulation parameters, serum biochemistry, gross anatomy, and histopathological examination of all Sprague-Dawley (SD) rats after intravenous administration of single or multiple doses of PAA@IONs showed no abnormal findings. Therefore, the ultrasmall superparamagnetic iron oxide nanoparticles constructed herein are a promising contrast agent for nodal tumor staging.