Introduction: This study investigates the oxidative stress responses induced by polystyrene nanoplastics (PS-NPs) across three distinct biological models—Aurelia coerulea polyps, BV2 microglial cells, and ICR (Institute of Cancer Research) mice. We aimed to explore the involvement of the mitogen-activated protein kinase (MAPK) signaling pathway as a potential mechanism in invertebrate and cellular systems, while evaluating neurobehavioral outcomes in vivo.Methods: Oxidative stress markers including catalase (CAT), total antioxidant capacity (T-AOC), and malondialdehyde (MDA) were quantified in all the three models. Transcriptomic analysis and RT-qPCR validation targeting the MAPK signaling pathway were performed in Aurelia coerulea polyps and BV2 microglial cells. Behavioral assessments, including the open field test and novel object recognition test, were conducted in mice to evaluate anxiety-like behavior and cognitive impairment following PS-NPs exposure.Results: In polyps, PS-NPs exposure resulted in shortened tentacle length and a dose-dependent decrease in T-AOC and CAT activity, along with an increase in MDA levels, indicating oxidative stress. BV2 microglia exhibited intracellular PS-NP accumulation, increased reactive oxygen species (ROS), upregulated inflammatory cytokines, and elevated apoptosis. Transcriptome analysis revealed significant activation of the MAPK signaling pathway in both polyps and BV2 cells. In mice, PS-NPs caused reduced central zone exploration and lower discrimination index scores, consistent with anxiety-like behavior and cognitive dysfunction. Immunohistochemical staining revealed microglial activation in the hippocampus, exhibiting the neurotoxic effects of PS-NPs.Discussion: While these models represent distinct organisms and biological contexts, all demonstrated consistent oxidative stress responses upon PS-NPs exposure. Although we do not claim direct equivalency across species, the converging evidence from marine, cellular, and mammalian systems highlights the widespread biological risks posed by nanoplastics. These findings provide a foundation for evaluating environmental and public health threats associated with PS-NPs.

Reducing Ca²⁺ content in the sarcoplasmic reticulum (SR) through ryanodine receptors (RyRs) by calcin is a potential intervention strategy for the SR Ca²⁺ overload triggered by β-adrenergic stress in acute heart diseases. OpiCal-PEG-PLGA nanomicelles were prepared by thin film dispersion, of which the antagonistic effects were observed using an acute heart failure model induced by epinephrine and caffeine in mice. In addition, cardiac targeting, self-stability as well as biotoxicity were determined. The synthesized OpiCa1-PEG-PLGA nanomicelles were elliptical with a particle size of 72.26 nm, a PDI value of 0.3, and a molecular weight of 10.39 kDa. The nanomicelles showed a significant antagonistic effect with 100 % survival rate to the death induced by epinephrine and caffeine, which was supported by echocardiography with significantly recovered heart rate, ejection fraction and left ventricular fractional shortening rate. The FITC labeled nanomicelles had a strong membrance penetrating capacity within 2 h and cardiac targeting within 12 h that was further confirmed by immunohistochemistry with a self-prepared OpiCa1 polyclonal antibody. Meanwhile, the nanomicelles can keep better stability and dispersibility in vitro at 4 °C rather than 20 °C or 37 °C, while maintain a low but stable plasma OpiCa1 concentration in vivo within 72 h. Finally, no obvious biotoxicities were observed by CCK-8, flow cytometry, H&E staining and blood biochemical examinations. Our study also provide a novel nanodelivery pathway for targeting RyRs and antagonizing the SR Ca²⁺ disordered heart diseases by actively releasing SR Ca²⁺ through RyRs with calcin.