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Accumulation of triphenylphosphonium (TPP) is normally observed in the mitochondria from the extracellular spaces due to the high difference in plasma membrane potential of the mitochondria. In the cancer cells, the mitochondrial membrane potential gap is higher as compared to that of normal cells resulting in elevated uptake of TPP. Silica nanoparticles (SNPs) being widely developed and used for biomedical applications, in this study, we tried to modify the surface of SNPs with varying amounts of TPP to verify their possible application as a positron emission tomography (PET) agent. The studies confirmed that the high level of TPP loading on the surface of SNPs possess higher positive charge (+ 31.5 mV). Owing to this behavior of plasma membrane potential of cancerous cells the uptake of positively charged SNPs was much higher in tumor cells than that of normal cells which was confirmed by PET imaging. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]