A Calixarene Assembly Strategy of Combined Anti-Neuroinflammation and Drug Delivery Functions for Traumatic Brain Injury Therapy.

Excessive inflammatory reaction aggravates brain injury and hinders the recovery of neural function in nervous system diseases. Microglia, as the major players of neuroinflammation, control the progress of the disease. There is an urgent need for effective non-invasive therapy to treat neuroinflammation mediated by microglia. However, the lack of specificity of anti-inflammatory agents and insufficient drug dose penetrating into the brain lesion area are the main problems. Here, we evaluated a series of calixarenes and found that among them the self-assembling architecture of amphiphilic sulfonatocalix[8]arene (SC8A12C) had the most potent ability to suppress neuroinflammation in vitro and in vivo. Moreover, SC8A12C assemblies were internalized into microglia through macropinocytosis. In addition, after applying the SC8A12C assemblies to the exposed brain tissue, we observed that SC8A12C assemblies penetrated into the brain parenchyma and eliminated the inflammatory factor storm, thereby restoring neurobiological functions in a mouse model of traumatic brain injury.

Receptor-targeting nanomaterials alleviate binge drinking-induced neurodegeneration as artificial neurotrophins.

The distinguished properties of nanomaterials promote us to explore whether their intrinsic activities would be beneficial to disease treatment. Furthermore, understanding the molecular mechanism is thereby crucial for biomedical applications. Here, we investigate the therapeutic effects of single-walled carbon nanotubes (SWNTs) in a rat model of binge alcohol-induced neurodegeneration. With selection from four types of SWNT structures, bundled SWNTs (bSWNTs) facilitated the recovery of learning and memory via enhancing neuroprotection and neuroregeneration. We screened the potential target for bSWNTs, and found that bSWNTs have the abilities to directly interact with neurotrophic receptors, especially tropomyosin-related kinase B (TrkB). Moreover, similar to the actions of endogenous neurotrophins, bSWNTs could trigger the dimerization and phosphorylation of TrkB, while these conformational changes resulted in activating their downstream signals involved in neuroprotection and neuroregeneration. With relatively clear mechanisms, these "artificial neurotrophins" provide a proof-of-concept example as an efficiently therapeutic strategy for the treatment of neurodegenerative diseases.

Synthesis of Diboronic Acid-Based Fluorescent Probes for the Sensitive Detection of Glucose in Aqueous Media and Biological Matrices.

Reliable and accurate glucose detection in biological samples is of great importance in clinical diagnosis and medical research. Chemical probes are advantageous in simple operation and flexible design, especially for the development of fluorescent probes. Anthracene-based diboronic acid (P-DBA) has shown potential in glucose probing because of its high sensitivity. However, poor solubility limits its applications in aqueous media. In this work, we systemically modify P-DBA by introducing fluoro (F-), chloro (Cl-), methoxyl (MeO-), or cyano (CN-) substituents. Among these probes, the cyano-substituted probe (CN-DBA) displays the highest glucose-binding constant (6489.5 M-1, 33% MeOH). More importantly, it shows good water solubility in the aqueous solution (0.5% MeOH), with ultrasensitive recognition with glucose (LOD = 1.51 µM) and robust sensing from pH 6.0 to 9.0. Based on these features, the CN-DBA is finally applied to detect glucose in cell lysates and plasma, with satisfactory recovery and precision. These results demonstrate that CN-DBA could serve as an accurate, sensitive fluorescent probe for glucose assays in biological samples.