process due to the aggressivity (e.g., electroporation or sonication methods), low yield, or poor controllability of traditional methods. [2,3] In addition, because the separation process from donor cells involves cumbersome processing steps, the weakened or lost function of exosomes in this process is difficult to be enhanced or compensated in the process of engineering. [4] In this work, the concept of "independent module/cascading function" is proposed for the controllable construction of engineered exosomes, that is, nanosized artificial module with specific functions is synthesized independently, and then selectively and controllably combined with natural exosome module in a "one-by-one" way to construct engineered exosome. The concept of "independent module" is not limited by the activity conditions of exosomes, so as to greatly enrich the preparation methods and types of artificial modules. Meantime, based on the selective and controllable combination technology between different modules, this method can effectively protect the integrity of exosome membrane structure and the activity of functional proteins and nucleic acids on membrane surface. "Cascading function" refers to endowing exosomes with new functions through rich design of artificial modules, and meeting the complex requirements of disease treatment through cascading effect, so as to play a remarkable therapeutic effect.In addition, this kind of engineered exosomes is applied to the treatment of Parkinson's disease (PD), aiming to solve the challenges of precise targeting and complex needs of PD treatment, of which the pathogenesis is complex and involves many factors and there is no effective method to completely cure it. [5] Up to now, the pathogenesis of PD can be summarized as the following process: nuclear gene mutation of dopaminergic neurons inhibits the normal hydrolysis of α-synuclein (α-syn) and promotes its aggregation in mitochondria, producing high concentration of reactive oxygen species (ROS), which further leads to enhanced expression of inducible nitric oxide synthase (iNOS) and neuroinflammation, and destroys itself and its surrounding neuronal cells. [6] Exosomes derived from stem cells have the potential to promote tissue repair and nerve regeneration, and have the ability to penetrate the blood-brain barrier Current exosome engineering methods usually lead to the damage of exosome morphology and membrane, which cannot meet the complex needs of disease treatment. Herein, the concept of an "independent module/cascading function" is proposed to construct an engineered exosome nanotherapy platform including an independent artificial module and a natural module. The artificial module with movement/chemotaxis function is first synthesized, and then it is controllably combined with the natural exosome module with "one by one" mode through a "differentiated" modification method. The whole process can not only maintain the activity of the natural exosome module, but also endows it with motion ability, so as to realize the purpose of...

The major challenges of immunotherapy for glioblastoma are that drugs cannot target tumor sites accurately and properly activate complex immune responses. Herein, we design and prepare a kind of chemotactic nanomotor loaded with brain endothelial cell targeting agent angiopep-2 and anti-tumor drug (Lonidamine modified with mitochondrial targeting agent triphenylphosphine, TLND). Reactive oxygen species and inducible nitric oxide synthase (ROS/iNOS), which are specifically highly expressed in glioblastoma microenvironment, are used as chemoattractants to induce the chemotactic behavior of the nanomotors. We propose a precise targeting strategy of brain endothelial cells-tumor cells-mitochondria. Results verified that the released NO and TLND can regulate the immune circulation through multiple steps to enhance the effect of immunotherapy, including triggering the immunogenic cell death of tumor, inducing dendritic cells to mature, promoting cytotoxic T cells infiltration, and regulating tumor microenvironment. Moreover, this treatment strategy can form an effective immune memory effect to prevent tumor metastasis and recurrence.

No abstract

Recombinant granulocyte colony-stimulating factor (G-CSF), with a direct repair effect on injured cardiomyocytes against myocardial infarction ischemia-reperfusion-injury (IRI), displays a poor effect owing to the limited cardiac targeting efficacy. There are almost no reports of nanomaterials that deliver G-CSF to the IRI site. Herein, we propose a way to protect G-CSF by constructing one layer of nitric oxide (NO)/hydrogen sulfide (H2S) nanomotors on its outside. NO/H2S nanomotors with specific chemotactic ability to high expression of reactive oxygen species (ROS)/induced nitric oxide synthase (iNOS) at the IRI site can deliver G-CSF to the IRI site efficiently. Meanwhile, superoxide dismutase is covalently bound to the outermost part, reducing ROS at the IRI site through a cascade effect with NO/H2S nanomotors. The synergistic effect between NO and H2S on the effective regulation of the IRI microenvironment can not only avoid toxicity caused by excessive concentration of a single gas but also reduce inflammation level and relieve calcium overload, so as to promote G-CSF to play a cardioprotective role.

Mercury enters the human body through the food chain and various ways and exists in blood, kidney and other organs, which will cause great harm. Therefore, it is important to design a safe and effective mercury remover for the removal of blood mercury. In this work, we modified a layer of amino‐rich hyperbranched polyamide nanomaterials (HPN) on the surface of Fe3O4 nanoparticles (Fe/HPN‐NH2 NPs). Among them, tetraethylenepentamine was crosslinked with hyperbranched polyamide by methyl acrylate, which effectively increased the number of amino functional groups in the material. The morphology, structural characteristics and composition of Fe/HPN‐NH2 NPs were characterized. The results of adsorption experiments showed that Fe/HPN‐NH2 NPs had good adsorption ability for inorganic mercury and methylmercury in water. Series of in vitro biocompatibility evaluation tests such as coagulation time tests, erythrocyte morphology observation, blood routine test, complement activation and immune factor test at the molecular level showed that the synthesized Fe/HPN‐NH2 NPs had good biocompatibility. When the initial concentration of lead was 1 ppm and the concentration of adsorbent was 10 mg/mL, the removal efficiency of blood mercury can reach up to 65 % without changing the amount of other commonly existing ions. This blood mercury removal strategy provides the possibility for blood purification.