Insight into the Internal Structure of High-Performance Multicore Magnetic Nanoparticles Used in Cancer Thermotherapy
Abstract
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
inter-laboratory and multi-modality 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. 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
Origin | Files produced by the author(s) |
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