Cerebral vasculature and neuronal networks will be largely destroyed due to the oxidative damage by overproduced reactive oxygen species (ROS) during a stroke, accompanied by the symptoms of ischemic injury and blood-brain barrier (BBB) disruption. Ceria nanoparticles, acting as an effective and recyclable ROS scavenger, have been shown to be highly effective in neuroprotection. However, the brain access of nanoparticles can only be achieved by targeting the damaged area of BBB, leading to the disrupted BBB being unprotected and to turbulence of the microenvironment in the brain. Nevertheless, the integrity of the BBB will cause very limited accumulation of therapeutic nanoparticles in brain lesions. This dilemma is a great challenge in the development of efficient stroke nanotherapeutics. Herein, we have developed an effective stroke treatment agent based on monodisperse ceria nanoparticles, which are loaded with edaravone and modified with Angiopep-2 and poly(ethylene glycol) on their surface (E-A/P-CeO). The as-designed E-A/P-CeO features highly effective BBB crossing via receptor-mediated transcytosis to access brain tissues and synergistic elimination of ROS by both the loaded edaravone and ceria nanoparticles. As a result, the E-A/P-CeO with low toxicity and excellent hemo/histocompatibility can be used to effectively treat strokes due to great intracephalic uptake enhancement and, in the meantime, effectively protect the BBB, holding great potentials in stroke therapy with much mitigated harmful side effects and sequelae.

The mononuclear phagocyte system (MPS, e.g., liver and spleen) is often treated as a 'blackbox' by nano-researchers in translating nanomedicines. Often, most of the injected nanomaterials are sequestered by the MPS, preventing their delivery to the desired disease areas. Here, we exploit this imperfection by applying nano-antioxidants with preferential liver uptake to directly prevent hepatic ischemia-reperfusion injury (IRI), which is a reactive oxygen species (ROS)related disease. Ceria nanoparticles (NPs) were selected as a representative nano-antioxidant and detailed mechanism of preventing IRI was investigated. We found that ceria NPs effectively alleviated the clinical symptoms of hepatic IRI by scavenging ROS, inhibiting activation of Kupffer cells and monocyte/macrophage cells. The released pro-inflammatory cytokines were then significantly reduced and the recruitment and infiltration of neutrophils were minimized, which suppressed subsequent inflammatory reaction involved in the liver. The protective effect of nanoantioxidants against hepatic IRI in living animals and the revealed mechanism herein suggests their future use for the treatment of hepatic IRI in the clinic.

Cancer immunotherapy shows promising potential in future cancer treatment but unfortunately is clinically unsatisfactory due to the low therapeutic efficacy and the possible severe immunotoxicity. Here we show a combined magnetic hyperthermia therapy (MHT) and checkpoint blockade immunotherapy for both primary tumor ablation and mimetic metastatic tumor inhibition. Monodispersed, high-performance superparamagnetic CoFe2O4@MnFe2O4 nanoparticles were synthesized and used for effective MHT-induced thermal ablation of primary tumors. Simultaneously, numerous tumor-associated antigens were produced to promote the maturation and activation of dendritic cells (DCs) and cytotoxic T cells for effective immunotherapy of distant mimetic metastatic tumors in a tumor-bearing mice model. The combined MHT and checkpoint blockade immunotherapy demonstrate the great potentials in the fight against both primary and metastatic tumors.