Dynamic Fractal Ice Nano-Nucleators for Cancer Cryotherapy

We present cryo-responsive dynamic fractal ice nano-nucleators (DF-INNs) for cryo-cancer therapy applications. Our development of DF-INNs leverages their structural advantages, which inherently maximizes the number of active sites for heterogeneous ice nucleation. Owing to their radially attached nanocrystalline structure, DF-INNs expose an extensive array of grain boundaries. The rapid precipitation and subsequent radial attachments of nanocrystallites promote the exposure of facets with high Miller indices, intrinsically strained, five-fold twinned nanocrystals, and increasing point defects due to kinetically-limited precipitation. This unique fractal structure culminates in the elevating of freezing temperature compared to Euclidean-shaped ice nucleators. Additionally, the branched fractal structure of DF-INNs facilitates heterogenic ice formation within its nanoconfined region, leading to the production of numerous self-similar small fractal fragments. This fragmentation is primarily driven by nanoconfinement-induced delayed ice nucleation, similar to frost heaving. The shear stress can be easily relieved through grain boundary sliding within the radially stacked DF-INN, making itself prone to cryo-responsive fragmentation. Such dynamic attributes significantly enhance ice nucleating activity, presenting a powerful strategy to increase the efficacy of cryotherapy by enhancing cellular ice formation and in vivo tumor coverage.