Cardiovascular diseases with severe vascular stenosis or occlusion can lead to tissue hypoxia, multi-organ dysfunction, and high mortality, emphasizing the need for accurate and safe vascular imaging. While digital subtraction angiography and computed tomography angiography are widely used, they involve ionizing radiation and iodinated contrast agents, posing risks of nephrotoxicity and allergic reactions. Contrast-enhanced magnetic resonance angiography (CE-MRA) offers a non-ionizing alternative, but gadolinium-based agents are limited by rapid clearance, risks of nephrogenic systemic fibrosis, and CNS accumulation. Metal-doped superparamagnetic iron oxide nanoparticles (SPIONs) represent promising T₁ probes; however, conventional surface coatings often increase hydrodynamic size, limiting renal clearance. Here, we develop ultrasmall MnFe₂O₄ nanoparticles functionalized with zwitterionic dopamine sulfonate (ZDS), exhibiting excellent water solubility, high longitudinal relaxivity (R₁ = 5.47 mM⁻¹·s⁻¹), and a compact hydrodynamic diameter (~ 6 nm) suitable for renal elimination. Under clinical 3.0 T MRI, ZDS@MnFe₂O₄ enables high-resolution imaging of cervical and abdominal vasculature, resolving vessels as small as 0.38 mm up to 1-h post-injection. The outstanding imaging capability allows real-time monitoring of carotid recanalization and detection of acute superior mesenteric veins and deep vein thromboses. This platform offers a promising approach for advanced vascular diagnostics by striking an optimal balance among imaging performance, biosafety, and clinical practicality.

Gold nanoparticles (AuNPs) assembled with fluorescent peptides through Au-S bonds (pep-AuNPs) have been widely used in biomolecular detection. However, due to the endo/lysosomal trapping after the nanoprobes enter cells, the direct delivery of AuNP probes into the cytoplasm for real-time imaging remains a difficult barrier for many cytoplasm-targeting agents. Here, we prepare AuNP@gel by wrapping a multi-functional nanogel structure on the surface of a single AuNP probe by in-situ polymerization in order to directly deliver AuNP probes into the cell cytoplasm. Compared with the pep-AuNP probes, which are trapped inside lysosomes for long periods, the AuNP@gel probes use the proton-sponge effect to effectively disrupt endo/lysosomal membranes and remain in the cytoplasm. In addition, the AuNP@gel probes rapidly escape from endo/lysosomes to avoid the complex environment that interferes with the stability of the AuNP probes and the lysosomal-storage trigger the upregulation of oxidative stress into the cells. The nanogel structure enables the AuNP probes to avoid some detrimental effects and to achieve high-fidelity fluorescence signals in the cells. Compared to traditional strategies for lysosomal escape, this one-step in-situ polymerization procedure avoids the complicated modification of additional ligands and is generally applicable to peptide-, DNA-, and polymer-linked AuNP probes.