3D-imaging and quantitative assessment for size-related penetration of HfO2 nanoparticles in breast cancer tumor by synchrotron radiation microcomputed tomography

Abstract

The development of quantitative analytical methods to assess the heterogeneous distribution and penetration of nanodrugs in solid tumors is of great importance for anticancer nanomedicine. Herein, Expectation-Maximization (EM) iterate algorithm and threshold segmentation methods were used to visualize and quantify the spatial distribution patterns, penetration depth and diffusion features of two-sized hafnium oxide nanoparticles (s-HfO₂ NPs in 2 nm and l-HfO₂ NPs in 50 nm sizes) in mouse models of breast cancer using synchrotron radiation micro-computed tomography (SR-μCT) imaging technique. The three-dimensional (3D) SR-μCT images were reconstructed based on the EM iterate algorithm thus clearly displayed the size-related penetration and distribution within the tumors after intra-tumoral injection of HfO₂ NPs and X-ray irradiation treatment. The obtained 3D animations clearly show that a considerable amount of s-HfO₂ and l-HfO₂ NPs diffused into tumor tissues at 2 h post-injection and displayed the obvious increase in the tumor penetration and distribution area within the tumors at day 7 after combination with low-dose X-ray irradiation treatment. A thresholding segmentation for 3D SR-μCT image was developed to assess the penetration depth and quantity of HfO₂ NPs along the injection sites in tumors. The developed 3D-imaging techniques revealed that the s-HfO₂ NPs presented more homogeneous distribution pattern, diffused more quickly and penetrated more deeply within tumor tissues than the l-HfO₂ NPs did. Whereas, the low-dose X-ray irradiation treatment greatly enhanced the wide distribution and deep penetration of both s-HfO₂ and l-HfO₂ NPs. This developed method may provide quantitative distribution and penetration information for the X-ray sensitive high-Z metal nanodrugs in the cancer imaging and therapy.