A mitochondrion-targeted poly(N-isopropylacrylamide-coacrylic acid) nanohydrogel with a fluorescent bioprobe for ferrous ion imaging in vitro and in vivo.

An imbalance in iron homeostasis contributes to mitochondrial dysfunction, which is closely linked to the pathogenesis of various diseases. Herein, we developed a nanosensor for detecting mitochondrial ferrous ions in vitro and in vivo. A poly(N-isopropylacrylamine)-coacrylic acid nanohydrogel was synthesized, and ferrous ions were detected using the fluorescent probe FeRhonox-1 embedded within it. (3-Carboxypropyl)-triphenylphosphonium bromide was chemically conjugated to the hydrogel matrix to enable mitochondrial targeting. The developed nanosensor showed a narrow particle size distribution, high sensitivity and selectivity for ferrous ions, and low cytotoxicity, enabling the nanosensor to sense and image ferrous ions in mitochondria with high spatial resolution. Changes in ferrous ion concentrations in human umbilical vein endothelial cells were measured and imaged after lipopolysaccharide (LPS) or iron dextran treatment. Moreover, the nanosensor was successfully used for ferrous ion imaging in live mice. The in vivo results showed that LPS injection induced the accumulation of mitochondrial ferrous ions. The proposed nanosensor could serve as a powerful tool for monitoring ferrous ions in mitochondria, providing strong support for studying disorders of iron metabolism.