Drug-Loaded Zwitterion-Based Nanomotors for the Treatment of Spinal Cord Injury.

Spinal cord injury (SCI) treatment requires a nanosystem for drug delivery that can effectively penetrate the blood-spinal cord barrier (BSCB). Herein, we designed poly(2-methacryloyloxyethyl phosphorylgallylcholine) (PMPC)/l-arginine (PMPC/A)-based nanomotors that can release nitric oxide (NO). The nanomotors were loaded with the inducible NO synthase inhibitor 1400W and nerve growth factor (NGF). PMPC with a zwitterionic structure not only provided good biocompatibility for the nanomotors but also facilitated their passage through the BSCB owing to the assistance of a large number of choline transporters on the BSCB. Additionally, the l-arginine loaded on the nanomotors was able to react with reactive oxygen species in the microenvironment of the injured nerve to produce NO, thereby conferring the ability of autonomic movement to the nanomotors, which facilitated the uptake of drugs by cells in damaged areas and penetration in pathological tissues. Moreover, in vivo animal experiments indicated that the PMPC/A/1400W/NGF nanomotors could effectively pass through the BSCB and restore the motion function of a rat SCI model by regulating its internal environment as well as the release of therapeutic drugs. Thus, the drug delivery system based on nanomotor technology offers a promising strategy for treating central nervous system diseases.

A nitric-oxide driven chemotactic nanomotor for enhanced immunotherapy of glioblastoma.

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.

Facile Microwave Synthesis of a Narrow-Band Green-Emitting Phosphor Cs3MnBr5 and the Effect of Anion Substitution on Its Luminescence Properties.

A bright blue light excitable and narrow-band green-emitting phosphor Cs3MnBr5 has been synthesized by a facile microwave radiation method within 2 min. The influence of the matrix on its steady-state and transient-state luminescence properties is investigated by partial substitution of Br- ions by Cl- ions. The incorporation of Cl- ions in Cs3Mn(Br1-xClx)5 resulted in almost no change in the emission maxima of Mn2+, which is attributed to the synergistic effect of reduced covalency and increased crystal field strength caused by the replacement of Br- ions by Cl- ions. Meanwhile, the emission of Mn2+ decreases with the increasing Cl- content, which is caused by different thermal quenching of Mn2+ emission in the mixed Cl-/Br- coordination. Moreover, the incorporation of Cl- in Cs3Mn(Br1-xClx)5 was found to have different effects on the lifetime of Mn2+ at different temperatures, that is, at room temperature, the lifetime of Mn2+ decreases with the increasing Cl- content, while at liquid nitrogen temperature, the lifetime of Mn2+ increases upon increasing the Cl- content. The former is due to the different thermal quenching for different coordinations of Mn2+ with Cl- and Br-, while the latter is due to the weaker spin-orbit coupling of the Mn2+ ion caused by the interaction with the lighter Cl- ions, which makes the spin selection rule stricter and leads to a longer lifetime of Mn2+ consequently.

Nitric oxide-driven nanomotors with bowl-shaped mesoporous silica for targeted thrombolysis.

Vein thrombosis is one of the most serious types of cardiovascular disease. During the traditional treatment, due to the excessive blood flow rate, the drug utilization rate at the thrombus site is low and the thrombolysis efficiency is poor. In this study, bowl-shaped silica nanomotors driven by nitric oxide (NO) are designed to target the thrombus surface by modifying arginine-glycine-aspartic acid (RGD) polypeptide, and simultaneously loading l-arginine (LA) and thrombolytic drug urokinase (UK) in its mesopore structure. LA can react with excessive reactive oxygen species (ROS) in the thrombus microenvironment to produce NO, thus promoting the movement of nanomotors to improve the retention efficiency and utilization rate of drugs in the thrombus site, and at the same time achieve the effect of eliminating ROS and reducing the oxidative stress of inflammatory endothelial cells. The loaded UK can dissolve thrombus quickly. It is worth mentioning that NO can not only be used as a power source of nanomotors, but also can be used as a therapeutic agent to stimulate the growth of endothelial cells and reduce vascular injury. This therapeutic agent based on nanomotor technology is expected to provide support for future research on thrombus treatment.

Zwitterion-Based Hydrogen Sulfide Nanomotors Induce Multiple Acidosis in Tumor Cells by Destroying Tumor Metabolic Symbiosis.

Destruction of tumor metabolism symbiosis is an attractive cancer treatment method which targets tumor cells with little harm to normal cells. Yet, a single intervention strategy and poor penetration of the drug in tumor tissue result in limited effect. Herein, we propose a zero-waste zwitterion-based hydrogen sulfide (H2 S)-driven nanomotor based on the basic principle of reaction in human body. When loaded with monocarboxylic acid transporter inhibitor α-cyano-4-hydroxycinnamic acid (α-CHCA), the nanomotor can move in tumor microenvironment and induce multiple acidosis of tumor cells and inhibit tumor growth through the synergistic effect of motion effect, driving force H2 S and α-CHCA. Given the good biosafety of the substrate and driving gas of this kind of nanomotor, as well as the limited variety of nanomotors currently available to move in the tumor microenvironment, this kind of nanomotor may provide a competitive candidate for the active drug delivery system of cancer treatment.

Na+-functionalized carbon dots with aggregation-induced and enhanced cyan emission.

A new type of carbon dots that emit blue emission in aqueous state while cyan emission in solid state was synthesized by a simple hydrothermal method. The photoluminescence quantum yield of the carbon dots in aqueous state and solid state is 7.6% and 29.2%, respectively. The enhanced and red-shifted emission observed in solid state carbon dots is ascribed to surface state change caused by aggregation. The occurrence of surface state change in solid state carbon dots has been evidenced by concentration dependent steady-state photoluminecence spectra and time-resolved luminescence decay. Surface functionalization by Na+ is beneficial for carbon dots to resist luminescence quenching in solid state. A proof-of-concept study was performed to demonstrate the potential application of the obtained carbon dots as inks for anti-counterfeiting and printing high quality fluorescent images.