Roussel Tom, Ferry Daniel, Kosta Artemis, Miele Dalila, Sandri Giuseppina, Tansi Felista L, Steiniger Frank, Southern Paul, Pankhurst Quentin A, Peng Ling, Giorgio Suzanne
Aix-Marseille Université, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille, Equipe Labellisée Ligue Contre le Cancer, 13288 Marseille, France.
Aix-Marseille Université, CNRS, Institut de Microbiologie de la Méditerranée, 13009 Marseille, France.
ACS Mater Au. 2024 Aug 16;4(5):489-499. doi: 10.1021/acsmaterialsau.4c00021. eCollection 2024 Sep 11.
Multicore magnetic nanoparticles (MNPs), comprising iron oxide cores embedded in a sugar or starch matrix, are a class of nanomaterials with promising magnetic heating properties. Their internal structure, and particularly the strength of the internal core-core magnetic interactions, are believed to determine the functional properties, but there have been few detailed studies on this to date. We report here on an interlaboratory and multimodality transmission electron microscopy (TEM) and magnetic study of a high-performance MNP material (supplied by Resonant Circuits Limited, RCL) that is currently being used in a clinical study for the treatment of pancreatic cancer. TEM data were collected under a variety of conditions: conventional; high-resolution; scanning; cryogenic; and, for the first time, liquid phase. All the imaging modes showed mostly irregular dextran lamellae of lateral dimensions 30-90 nm, plus ca. 15% n/n of what appeared to be 30-60 nm long "nanorods", and a multitude of well-dispersed ca. 3.7 nm diameter iron oxide cores. Cryogenic electron tomography indicated that the nanorods were edge-on lamellae, but in dried samples, tomography showed rod- or lath-shaped forms, possibly resulting from the collapse of lamellae during drying. High-resolution TEM (HRTEM) showed the dextran to be crystallized in the low-temperature hydrated dextran polymorph. Magnetic remanence Henkel-plot analysis indicated a weak core-core interaction field of ca. 4.8 kA/m. Theoretical estimates using a point-dipole model associated this field with a core-to-core separation distance of ca. 5 nm, which tallies well with the ca. 4-6 nm range of separation distances observed in liquid-cell TEM data. On this basis, we identify the structure-function link in the RCL nanoparticles to be the unusually well-dispersed multicore structure that leads to their strong heating capability. This insight provides an important design characteristic for the future development of bespoke nanomaterials for this significant clinical application.
多核磁性纳米颗粒（MNP）由嵌入糖或淀粉基质中的氧化铁核组成，是一类具有良好磁热性能的纳米材料。人们认为它们的内部结构，特别是内核-内核磁相互作用的强度，决定了其功能特性，但迄今为止对此进行的详细研究很少。我们在此报告了一项跨实验室的多模态透射电子显微镜（TEM）和磁性研究，该研究针对一种高性能MNP材料（由共振电路有限公司，RCL提供），该材料目前正在用于胰腺癌治疗的临床研究。在各种条件下收集了TEM数据：常规条件；高分辨率条件；扫描条件；低温条件；以及首次在液相条件下。所有成像模式大多显示出横向尺寸为30-90nm的不规则葡聚糖薄片，外加约15%（n/n）似乎是30-60nm长的“纳米棒”，以及大量分散良好的直径约3.7nm的氧化铁核。低温电子断层扫描表明纳米棒是边缘取向的薄片，但在干燥样品中，断层扫描显示为棒状或板条状形态，这可能是由于干燥过程中薄片的塌陷所致。高分辨率TEM（HRTEM）显示葡聚糖在低温水合葡聚糖多晶型中结晶。剩磁亨克尔图分析表明内核-内核相互作用场较弱，约为4.8kA/m。使用点偶极子模型的理论估计将该场与约5nm的核间距相关联，这与液池TEM数据中观察到的约4-6nm的间距范围非常吻合。在此基础上，我们确定RCL纳米颗粒中的结构-功能联系是异常分散良好的多核结构，这导致了它们强大的加热能力。这一见解为这种重要临床应用的定制纳米材料的未来开发提供了重要的设计特征。
