Insight into the Internal Structure of High-Performance Multicore Magnetic Nanoparticles Used in Cancer Thermotherapy

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.