Superparamagnetic Iron Oxide Nanoparticles with Large Magnetic Saturation and High Particle Photon Counts for Super-Resolution Imaging of Lysosomes

Superparamagnetic iron oxide nanoparticles (SPIONs) have become benchmark materials for their large magnetic saturation and excellent T₂ contrast. Despite the large magnetic saturation that arises due to the enormous iron content, incorporating a fluorescent nature for their use as multimodal probes drastically reduces the magnetic saturation. To achieve the desired magnetic saturation in fluorescence-decorated SPIONs, the size is increased substantially to hundreds of nanometers. Here, we rationally design fluorescent SPIONs of size ∼16 nm with significant magnetic saturation and high single-particle photon counts used for optical-based super-resolution microscopy. The SPIONs were highly specific to stain and image the lysosomes of HeLa cells with high contrast and were capable of providing super-resolution radial fluctuation (SRRF) imaging of lysosomes down to 130 nm, which is much lower than the diffraction limit in light microscopy.