One-pot synthesis of chelator-free ⁸⁹Zr-incorporated hierarchical hematite nanoclusters for in vitro evaluation

In biological applications of nanoparticles, the control of physicochemical properties such as size, shape, and surface charge enables the improvement of their ability for cancer target. In addition, it can be tracked by labeling in these nanoparticles with medical radionuclides for detection of cancer. Here, we report novel chelator-free direct-labeling of hierarchical hematite nanoclusters with ⁸⁹Zr (⁸⁹Zr-IONCs) through hydrothermal reaction to develop biocompatible radiolabeled nanoparticle which is effective for tracking cancer cells. Characterization of ⁸⁹Zr-IONCs revealed that the zirconium ions were tightly bound inside hematite crystals with intervals of glutamic acid absorbed on their surfaces having spindle shape with a mean width of 180 nm and length of 80 nm. This method showed promising radiolabeling yield and labeling stability in biological environments which was ≥ 99%. Their high colloidal stability in serum was considerably maintained for the span of a week by the formation of protein corona with the hematite nanoclusters. For the result of biological evaluations, cytotoxicity assay provides evidence of the high biocompatibility of the product. The elevated in vitro cellular uptake of ⁸⁹Zr-IONCs for the CT-26 and A549 cells was observed. Furthermore, we found that the spindle shape of ⁸⁹Zr-IONCs was more effective for cell internalization compared with round shape due to the extended interfacial surface area with a cell membrane when their endocytosis is started. Our one-pot synthesized ⁸⁹Zr-incorporated hematite nanoclusters show the promising approach for a simple and highly stable chelator-free radiolabeling system, which exploits the non-toxic potential carrier to target cancer cells.