Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra and the accumulation of α-synuclein in the brain. Ferroptosis, a recently identified form of regulated cell death, is critical in PD pathogenesis due to its association with iron deposition, overproduction of reactive oxygen species, iron-dependent lipid peroxidation and impaired lipid peroxidation clearance. This cell death mechanism is closely linked to several pathogenic processes in PD, including α-synuclein aggregation, oxidative stress, mitochondrial dysfunction, microglia-induced neuroinflammation, and neuromelanin accumulation. Given the significant role of ferroptosis in these mechanisms, there is increasing interest in targeting ferroptosis for PD treatment. Several drugs have shown potential in alleviating PD symptoms by inhibiting ferroptosis. This review aims to consolidate current knowledge on ferroptosis in PD and assess the therapeutic potential of anti-ferroptosis drugs, highlighting promising directions for future research and clinical applications.

The detection of lymph node metastasis is of great importance for therapy planning and prognosis of cancers, but remains challenging in the clinic. In the current study, we report a tumor-specific imaging probe constructed with NaGdF₄:Yb,Tm,Ca@NaLuF₄ core@shell upconversion nanoparticles showing distinctive near infrared emission. The following studies revealed that the characteristic Tm dopant emission at 804 nm showed a penetration depth up to 7.7 mm through multi-layered mice skin tissues, substantially greater than emissions at 655 nm and 541 nm typically from the widely used Er dopant, which is apparently favorable for sensitive tumor diagnosis. The cell binding assay further revealed that the anti-HER2 antibodies covalently attached on the particle surface endowed the nanoprobe with excellent binding specificity in targeting HER2-positive cancer cells in vitro, which further enabled the detection of lymph node metastasis of breast cancer in vivo in mice. In addition, the pharmacokinetics of the resulting nanoprobes were intensively studied through both upconversion luminescence imaging and SPECT imaging for comparing with that of the mother particles. The results obtained through both approaches were well consistent and revealed that the surface conjugation of antibodies largely altered the pharmacokinetic behaviors and substantially prolonged the blood half-life of the underlying nanoparticles, which was never reported before.

Hypoxia is a common biological condition in many malignant solid tumors that plays an imperative role in regulating tumor growth and impacting the treatment’s therapeutic effect. Therefore, the hypoxia assessment is of great significance in predicting tumor development and evaluating its prognosis. Among the plenty of existing tumor diagnosis techniques, magnetic resonance imaging (MRI) offers certain distinctive features, such as being free of ionizing radiation and providing images with a high spatial resolution. In this study, we develop a fluorescent traceable and hypoxia-sensitive T₁-weighted MRI probe (Fe₃O₄-Met-Cy5.5) via conjugating notable hypoxia-sensitive metronidazole moiety and Cy5.5 dye with ultrasmall iron oxide (Fe₃O₄) nanoparticles. The results of in vitro and in vivo experiments show that Fe₃O₄-Met-Cy5.5 has excellent performance in relaxivity, biocompatibility, and hypoxia specificity. More importantly, the obvious signal enhancement in hypoxic areas indicates that the probe has great feasibility for sensing tumor hypoxia via T₁-weighted MRI. These promising results may unlock the potential of Fe₃O₄ nanoparticles as T₁-weighted contrast agents for the development of clinical hypoxia probes.