Asymmetric Assembling of Iron Oxide Nanocubes for Improving Magnetic Hyperthermia Performance

Abstract

Magnetic hyperthermia (MH) based on magnetic nanoparticles (MNPs) is a promising adjuvant therapy for cancer treatment. Particle clustering leading to complex magnetic interactions affects the heat generated by MNPs during MH. The heat efficiencies, theoretically predicted, are still poorly understood because of a lack of control of the fabrication of such clusters with defined geometries and thus their functionality. This study aims to correlate the heating efficiency under MH of individually coated iron oxide nanocubes (IONCs) versus soft colloidal nanoclusters made of small groupings of nanocubes arranged in different geometries. The controlled clustering of alkyl-stabilized IONCs is achieved here during the water transfer procedure by tuning the fraction of the amphiphilic copolymer, poly(styrene-co-maleic anhydride) cumene-terminated, to the nanoparticle surface. It is found that increasing the polymer-to-nanoparticle surface ratio leads to the formation of increasingly large nanoclusters with defined geometries. When compared to the individual nanocubes, we show here that controlled grouping of nanoparticles-so-called "dimers" and "trimers" composed of two and three nanocubes, respectively-increases specific absorption rate (SAR) values, while conversely, forming centrosymmetric clusters having more than four nanocubes leads to lower SAR values. Magnetization measurements and Monte Carlo-based simulations support the observed SAR trend and reveal the importance of the dipolar interaction effect and its dependence on the details of the particle arrangements within the different clusters.

Keywords: Monte Carlo simulation; annealing; controlled colloidal clustering; iron oxide nanocubes; magnetic hyperthermia; poly(styrene-co-maleic anhydride); specific absorption rate.

Figure 1

Scheme of the clustering protocol using 20 nm core–shell iron oxide nanocubes. Representative TEM micrographs of IONCs@PScMA in water and just after they have been prepared at a ratio of (A) 16.5, (B) 33, (C) 50, and (D) 66 polymer chains/nm² of particle surface. (E–H) Collection of TEM images at higher magnification of dimers and trimers formed at the ratio of 33. (I) Schematic representation of the formation of soft colloidal nanoclusters.

Figure 2

Tuning the mean hydrodynamic diameter of clusters by different polymer amounts. Volume distribution of hydrodynamic size d_H of soft colloidal clusters measured in water starting from 20 nm IONCs. The d_H was adjusted between 38 and 99 nm. No aggregation of clusters was detected as PDI values were between 0.07 and 0.14 (see inset).

Figure 3

Statistical analysis of fractions of different objects for samples (A) 16.5PScMA, (B) 33PScMA, and (C) 66PScMA indicated the presence of (A) 32% 1D and 2D constructs (28% dimers and 4% trimers) in sample 16.5PScMA, (B) majority of 70% (35% dimers and 35% trimers) in sample 33PScMA, and (C) only 9% (5% dimers and 4% trimers) 1D and 2D structures in sample 66PScMA, with a majority of clusters with a number of nanocubes higher than 4 (86%).

Figure 4

(a) TGA weight-loss profiles of oleic-acid-capped IONCs (sample A, blue curve) and free oleic acid (violet curve) performed in air. The first weight loss in the region between 150 and 300 °C corresponded to free oleic acid in solution, and the second weight loss in the region between 300 and 400 °C corresponded to oleate chemisorbed to the surface of the IONCs. (b) TGA weight-loss profiles of a new batch of as-synthesized oleic-acid-capped IONCs (sample B, red curve) and sample B after washing to remove excess of oleic acid (green curve). On sample B, before washing, no clusters were obtained. Upon one washing, the amount of oleate decreased from 68.1 to 43.3 wt %, re-establishing the cluster formation on sample B.

Figure 5

SAR values for soft colloidal nanoclusters after 1 year aging time, formed at ratios of 16.5, 33, and 66 molecules PScMA/nm² of particle surface (f = 302 kHz, H = 23.8 kA/m). A higher SAR value was recorded for dimers and trimers compared to individual IONCs and clusters with n ≥ 4. Clustering the IONCs in centrosymmetric bead-like structures decreased their heating performance. Each experimental data point was calculated as the mean value of at least three independent measurements, with error bars indicating the mean deviation. Inset: SAR values obtained from kinetic Monte Carlo modeling of the structures as described in the text, reproducing the observed experimental trend within the error bar. Interparticle spacing for the simulation has been set to 1 nm gap as measured on the TEM images.

Figure 6

Magnetization hysteresis loops measured at room temperature (a,b), after cooling to 10 K in 5 T magnetic fields (c), and temperature-dependent zero-field-cooled and field-cooled magnetization measurements performed on aqueous suspension of nanoclusters after a year of aging time, solidified in gypsum matrix recorded at 50 Oe magnetic fields (d): 16.5PScMA (blue line, individual IONCs), 33PScMA (red line, dimers and trimers), and 66PScMA (green line, clusters with n ≥ 4).

Figure 7

Evolution of SAR values of soft colloidal nanoclusters by annealing in an oven at 80 °C. (A) SAR values (with standard deviation) for soft colloidal nanoclusters during the annealing process: individual IONCs, blue bars; dimers and trimers, red bars; and clusters with n ≥ 4, green bars. Only after 18 h of annealing did the sample of dimers and trimers show higher SAR values. The trend was maintained up to 52 h of annealing. (B) Schematic representation of the oxidation of the FeO core for clusters of different sizes in an oven at 80 °C.