Are cubic nanoparticles really better than spherical nanoparticles for magnetic hyperthermia?

• Cubic NPs are not always superior to spherical NPs for magnetic hyperthermia. • Dipolar interaction-induced chain formation improves heating efficiency in cubic and not spherical NPs. • Large spherical NPs can outperform cubic NPs due to reduced dipolar interactions. • Heating performance is a complex interplay between field parameters, concentration, and nanoparticle volume. • New guidelines to fairly compare NPs of different shapes. The practical applications of magnetic nanoparticles (NPs) for targeted heat and drug delivery have been hampered by a lack of fundamental understanding of the relationship between NP shape and heating efficiency. Existing approaches comparing the heating efficiency across different shapes are flawed because they do not account for magnetic volume differences in similarly sized NPs. Here, we establish the true relationship between shape and heating efficiency by synthesizing cubic and spherical NPs with different sizes but of similar magnetic volumes. Our findings reveal that the therapeutic outperformance of cubic over spherical NPs depends on their magnetic volumes, specific instrument parameters ( i.e., field strength and frequency), and concentration. Notably, cubic NPs outperform spherical NPs at low magnetic volumes at almost all tested field parameters. However, this is untrue at high magnetic volume, where the outperformance is observed to be more significantly impacted by the field conditions. In addition to the instrument parameters, NP concentration also affects outperformance (cube vs. sphere) but is not correlated with the magnetic properties of the NPs. Considering the effects of these parameters (e.g., magnetic volume, field parameters, concentration) on heating efficiency, our work provides a framework for designing, evaluating, and optimizing NP-based therapies with enhanced clinical efficacy. For magnetic hyperthermia, cubic nanoparticles are superior to spherical nanoparticles of the same magnetic volume. However, this assertion depends on the nanoparticle volume, concentration, and most importantly, instrument parameters ( i.e., field frequency and strength).