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

IF 5.7 2区 化学 Q1 CHEMISTRY, ANALYTICAL
Jiali Wang , Tingfeng Zhang , You Liao , Wei Chen , Shanshan Liang , Si Xu , Hao Fang , Meng Wang , Lingna Zheng , Zhanjun Gu , Zhiyong Zhang , Bing Wang , Yi Bi , Weiyue Feng
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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.

Abstract Image

同步辐射微计算机断层扫描对乳腺癌肿瘤中HfO2纳米颗粒尺寸相关穿透的3d成像和定量评估
发展纳米药物在实体肿瘤中的非均匀分布和渗透的定量分析方法对抗癌纳米药物具有重要意义。本文采用期望最大化(EM)迭代算法和阈值分割方法,利用同步辐射微计算机断层扫描(SR-μCT)成像技术,对两种尺寸的氧化铪纳米粒子(2 nm尺寸的s-HfO2 NPs和50 nm尺寸的l-HfO2 NPs)在乳腺癌小鼠模型中的空间分布模式、穿透深度和扩散特征进行可视化和量化。基于EM迭代算法重建三维(3D) SR μ ct图像,清晰显示肿瘤内注射HfO2 NPs和x射线照射治疗后肿瘤内与尺寸相关的穿透和分布。所获得的3D动画清晰显示,注射后2 h大量s-HfO2和l-HfO2 NPs弥散进入肿瘤组织,联合低剂量x射线照射治疗后第7天肿瘤穿透和肿瘤内分布面积明显增加。采用阈值分割方法对3D SR-μCT图像进行分割,评估HfO2 NPs沿肿瘤注射部位的渗透深度和数量。3d成像技术显示,与l-HfO2 NPs相比,s-HfO2 NPs在肿瘤组织内分布更均匀,扩散更快,渗透更深。而低剂量的x射线照射处理则大大增强了s-HfO2和l-HfO2 NPs的宽分布和深穿透。该方法可为x射线敏感高z金属纳米药物在肿瘤成像和治疗中的定量分布和穿透提供信息。
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来源期刊
Analytica Chimica Acta
Analytica Chimica Acta 化学-分析化学
CiteScore
10.40
自引率
6.50%
发文量
1081
审稿时长
38 days
期刊介绍: Analytica Chimica Acta has an open access mirror journal Analytica Chimica Acta: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. Analytica Chimica Acta provides a forum for the rapid publication of original research, and critical, comprehensive reviews dealing with all aspects of fundamental and applied modern analytical chemistry. The journal welcomes the submission of research papers which report studies concerning the development of new and significant analytical methodologies. In determining the suitability of submitted articles for publication, particular scrutiny will be placed on the degree of novelty and impact of the research and the extent to which it adds to the existing body of knowledge in analytical chemistry.
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