The treatment of Parkinson’s disease (PD) has been hindered by the complex pathologies and multiple membrane barriers during drug delivery. Although exosomes derived from mesenchymal stem cells (MSCs) have great potential for PD, MSC-derived exosomes alone could not fully meet the therapeutic requirements due to their limitation in therapy and delivery. Here, we develop a self-oriented nanocarrier called PR-EXO/PP@Cur that combines therapeutic MSC-derived exosomes with curcumin. PR-EXO/PP@Cur can be self-oriented across the multiple membrane barriers and directly release drugs into the cytoplasm of target cells after intranasal administration. With enhanced accumulation of drugs in the action site, PR-EXO/PP@Cur achieves three-pronged synergistic treatment to deal with the complex pathologies of PD by reducing α-synuclein aggregates, promoting neuron function recovery, and alleviating the neuroinflammation. After treatment with PR-EXO/PP@Cur, the movement and coordination ability of PD model mice are significantly improved. These results show that PR-EXO/PP@Cur has great prospects in treatment of PD or other neurodegenerative diseases.

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SummaryThe tuned liquid damper (TLD) and particle damper (PD) have been used as effective passive vibration absorbers to suppress undesirable structural vibrations induced by dynamic loads such as earthquake and strong winds. In this paper, through an integrated use of the TLD and PD, a new damper system named the tuned liquid particle damper (TLPD) was developed. The dynamic characteristics of TLPD in terms of tuning conditions and transfer functions were investigated through a series of shaking table tests. Nonlinear behaviors of TLPD in the frequency domain were discussed, and a preliminary framework was applied in the design of a five‐story steel frame building model using shaking table tests. Testing results confirmed the workability of the preliminary design framework as the primary structure is subjected to earthquake loadings. Performances of different TLPD‐structure systems were summarized from these testing programs. One of observations is that the TLPD system worked as a modified TLD in this study. The testing programs provide proof‐of‐concept results for this proposed vibration absorber.

Inspired by the fact that leukocytes have innate phagocytic functions and oriented migration capabilities in response to chemoattractants, we have unveiled that endogenous neutrophils as “Trojan horses”, participate in the delivery of nanoparticles in an “in vivo self-armed assembly” manner. Neutrophils were the main population to preferentially sequester the intravenous administrated nanoparticles with an average size of 260 nm. The pre-implantation of CXCL1-laden hydrogels could trigger and induce a targeted signal to attract an influx of neutrophils carrying the therapeutic goods to the desired position. In mouse models of melanoma, the combinatorial regimen of using the PLGA nanoparticles with the CXCL1 hydrogels exhibited superior tumor inhibition capability. This work leveraged the natural phagocytosis of neutrophile and the chemotactic effect of chemokines for targeted delivery. We believe this strategy will improve the therapeutic efficiency of nanoparticle-based delivery systems, especially when the chemokines are implanted at sites of surgical tumor removal, during cancer treatment at the clinic.

deficiencies such as instability and negative charge of the gene drug itself, some cationic polymers nanoparticles (NPs) have been designed and constructed to deliver gene drug. [2] However, given the special structure of brain, there are a series of tissue and cellular barriers during gene drug delivery for neurodegenerative diseases treatment. The bloodbrain barrier (BBB) and cell membrane barrier can lead to poor concentration of drugs in the lesion, which results in low therapeutic efficacy. [3] Besides, it cannot be ignored that the pathology of neurodegenerative diseases is often complicated. [4] In this work, PD, the second most common neurodegenerative diseases, is taken as an example. PD is characterized by the pathological deposition of α-synuclein (αsyn). [5] In addition, oxidative stress caused by elevated level of reactive oxygen species (ROS) can increase α-syn aggregation and promote parkinsonian pathology. [6] Studies have shown that small interfering RNA (siRNA) targeting SNCA (siSNCA) can downregulate the expression of α-syn protein to decrease the formation of α-syn aggregates. [7] However, it cannot directly alleviate the existing high ROS pathology.Ceria (CeO 2 ) nanozymes with diameter of 3-5 nm can efficiently scavenge ROS due to their large surface-to-volume ratio. [8] Additionally, different from polymers, the inorganic CeO 2 nanozymes with rigidity can enhance the surface roughness after modifying on the surface of NPs. It has been shown that the nanoscale surface roughness of the neurophilic viruses such as Japanese encephalitis virus, West Nile virus, and measles virus can lead to nonspecific binding forces that promote cellular uptake. [9] Besides, the glycoproteins on the surface of these viruses can promote the viruses to penetrate the BBB and target cells through specific receptor-ligand interaction. [10] Inspired by viruses and unique features of CeO 2 , we propose to construct self-catalytic siRNA nanocarriers for catalyzing delivery process and treatment process, thereby achieving efficient synergistic treatment. In addition, it is necessary to trace drugs accurately for guiding treatment.Herein, self-catalytic siRNA nanocarriers were constructed for catalyzing delivery process and treatment process to achieve efficient synergistic treatment of PD (Scheme 1a). First, the superparamagnetic iron oxide NPs (SPIONs), T 2 -weighted Gene therapy has shown great potential for neurodegenerative diseases with complex pathology. However, its therapeutic effect is limited due to the delivery barriers and its own single function. Herein, self-catalytic small interfering RNA (siRNA) nanocarriers (S/Ce-PABMS) are developed to catalyze delivery process and treatment process for synergistic treatment of neurodegenerative diseases. On the one hand, the rough surface of the S/Ce-PABMS mediated by ceria (CeO 2 ) nanozymes can catalyze cellular uptake in the delivery process, so that S/Ce-PABMS with acetylcholine analogs penetrate the blood-brain barrier and enter neurons more effectively. On...