As an oxygen-transporting protein, free hemoglobin (Hb) often suffers from the disadvantage of undesirable stability and short blood circulation, which severely impairs the potential clinical applications as the blood substitute. In this work, Hb was facilely encapsulated into a kind of metal−organic frameworks (MOFs) (ZIF-8) inspired by the natural biomineralization process. The obtained ZIF-8 encapsulating Hb (ZIF-8@Hb) showed the small hydrodynamic size of 180.8 nm and neutral zeta potential of −2.1 mV by adjusting the ratio of Hb in ZIF-8 frameworks. Intriguingly, Hb encapsulated by ZIF-8 exhibited significantly enhanced stability in alkaline, oxidation, high temperature, or enzymatic environment compared with free Hb because of the excellent protective MOF coatings. More importantly, the negative charge of Hb neutralized the original positive charge of ZIF-8, which led to the better biocompatibility, lower protein adsorption, and macrophage uptake of ZIF-8@Hb than bare ZIF-8 nanoparticles. Furthermore, ZIF-8@Hb displayed extended blood circulation with the elimination half-life of 13.9 h as well as reduced nonspecific distribution in normal organs compared with free Hb or ZIF-8 nanoparticles. With the above advantages, ZIF-8@Hb showed significantly extended survival time of mice in a disease model of hemorrhagic shock compared with free Hb or bare ZIF-8 nanoparticles. Overall, this work offers a high-stable and long-circulating oxygen carrier platform, which may find wide applications as a blood substitute to treat various oxygen-relevant diseases.

Local resection or ablation remains an important approach to treat drug-resistant central neurological disease. Conventional surgical approaches are designed to resect the diseased tissues. The emergence of photothermal therapy (PTT) offers a minimally invasive alternative. However, their poor penetration and potential off-target effect limit their clinical application. Here, polydopamine nanoparticles (PDA-NPs) were prepared and characterized. Studies were performed to evaluate whether PDA-NPs combined with near-infrared (NIR) light can be used to ablate deep brain structures in vitro and in vivo. PDA-NPs were prepared with a mean diameter of ∼150 nm. The particles show excellent photothermal conversion efficiency. PDA-NPs did not show remarkable cytotoxicity against neuronal-like SH-SY5Y cell lines. However, it can cause significant cell death when combined with NIR irradiation. Transcranial NIR irradiation after PDA-NPs administration induced enhanced local hyperthermia as compared with NIR alone. Local temperature exceeded 60 °C after 6 min of irradiation plus PDA while it can only reach 48 °C with NIR alone. PTT with PDA (10 mg/mL, 3 μL) and NIR (1.5 W/cm2) can ablate deep brain structures precisely with an ablation volume of ∼6.5 mm3. Histological analysis confirmed necrosis and apoptosis in the targeted area. These results demonstrate the potential of NP-assisted PTT for the treatment against nontumorous central neurological diseases.