A mix & act liposomes of phospholipase A2-phosphatidylserine for acute brain detoxification by blood‒brain barrier selective-opening.

In the treatment of central nervous system disease, the blood-brain barrier (BBB) is a major obstruction to drug delivery that must be overcome. In this study, we propose a brain-targeted delivery strategy based on selective opening of the BBB. This strategy allows some simple bare nanoparticles to enter the brain when mixed with special opening material; however, the BBB still maintains the ability to completely block molecules from passing through. Based on the screening of BBB opening and matrix delivery materials, we determined that phospholipase A2-catalyzed 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserine liposomes can efficiently carry drugs into the brain immediately. At an effective dose, this delivery system is safe, especially with its effect on the BBB being reversible. This mix & act delivery system has a simple structure and rapid preparation, making it a strong potential candidate for drug delivery across the BBB.

Negatively charged phospholipids doped liposome delivery system for mRNA with high transfection efficiency and low cytotoxicity.

Messenger RNA (mRNA) has become one of the most potential drugs in recent years. However, efficient and safe delivery of fragile and easily degradable mRNA is a major challenge. Appropriate delivery system (DS) determines the final effect of mRNA. Cationic lipids play a crucial and decisive role in the entire DS, but also cause huge biosafety problems due to the high toxicity. In this study, a new DS for mRNA delivery that combines negatively charged phospholipids was developed in order to neutralize the positive charge and thus increase the safety. Further, the factors affecting mRNA transfection from cell to animal were investigated. The mRNA DS with optimum condition of lipid composition, proportions, structure, and transfection time was synthesized. Adding an appropriate amount of the anionic lipid to liposomes could increase the safety while maintaining the original transfection efficiency. For transporting mRNA in vivo, requirements regarding the mRNA encapsulation and releasing rate should be further considered to optimize DS design and preparation.

Risk assessment based on dose-responsive and time-responsive genes to build PLS-DA models for exogenously induced lung injury.

Xenobiotics can easily harm human lungs owing to the openness of the respiratory system. Identifying pulmonary toxicity remains challenging owing to several reasons: 1) no biomarkers for pulmonary toxicity are available that might help to detect lung injury; 2) traditional animal experiments are time-consuming; 3) traditional detection methods solely focus on poisoning accidents; 4) analytical chemistry methods hardly achieve universal detection. An in vitro testing system able to identify the pulmonary toxicity of contaminants from food, the environment, and drugs is urgently needed. Compounds are virtually infinite, whereas toxicological mechanisms are countable. Therefore, universal methods to identify and predict the risks of contaminants can be designed based on these well-known toxicity mechanisms. In this study, we established a dataset based on transcriptome sequencing of A549 cells upon treatment with different compounds. The representativeness of our dataset was analyzed using bioinformatics methods. Artificial intelligence methods, namely partial least squares discriminant analysis (PLS-DA) models, were employed for toxicity prediction and toxicant identification. The developed model predicted the pulmonary toxicity of compounds with a 92 % accuracy. These models were submitted to an external validation using highly heterogeneous compounds, which supported the accuracy and robustness of our developed methodology. This assay exhibits universal potential applications for water quality monitoring, crop pollution detection, food and drug safety evaluation, as well as chemical warfare agent detection.

A fast-acting brain-targeted nano-delivery system with ultra-simple structure for brain emergency poisoning rescue.

Treatment for acute brain conditions remains a major challenge owing to the unavailability of antidotes, especially for organophosphorus compounds, exposure to which leads to rapid death. Despite recent advances in brain-targeted nano delivery systems (BTNDS), the traditional ones which have been developed will likely not lead to the quick release of an antidote, which is essential to counteract fast neurotoxic effects. Herein, we present a BTNDS using thermosensitive liposomes, without the need for functionalization, to obtain a platform for brain-targeted delivery, which has a simple structure and thus can be easily synthesized and scaled-up. The brain-targeting effect of BTNDS was amplified by phospholipase A2 (PLA2), an inflammatory biomarker. The combination of PLA2 and BTNDS significantly improved brain targeting, leading to an excellent emergency rescue effect - 83- and 4.8-fold better cerebral AChE reactivation response and survival time, respectively. These findings provide a promising strategy to generate a facile, druggable, and effective BTNDS.

Quantitative and qualitative analyses of metal ions in food and water by using a multicolor sensor array and chemometrics.

Rapid and accurate detection of toxic metal ions is the key to combating food contamination and environmental pollution. In sensor arrays, gold nanoparticles play a crucial role in monitoring metal ions based on surface plasmon resonance. However, identifying metal ions with unknown concentrations in a complex system through this assay is difficult because of its monotonous color change and weak anti-interference ability. To overcome these limitations, a sensitive, flexible, low-cost, and multicolor sensor array was designed herein. The applicability of the sensor array for the qualitative and quantitative analyses of metal ions in food and water was also verified. The developed sensor array could classify 14 metal ions (Cu2+, Fe2+, Fe3+, Mn2+, Ni2+, Zn2+, Cd2+, Cr3+, Co2+, Ba2+, K+, Tl+, Pb2+, and Hg2+) of unknown concentration with an accuracy of 100%. In addition, partial least squares models were established to quantify Tl+, Pb2+, and Hg2+ in water and rice samples, with square correlation coefficients (R2) of 0.9991, 0.9742, and 0.9731, respectively. This method can be used for accurate quantitative and qualitative analyses of heavy metal ions in water and food.

An in vitro nerve agent brain poisoning transwell model for convenient and accurate antidote evaluation.

Nerve agent (NA) can inhibit acetylcholinesterase (AChE) causing seriously injury at extremely low doses. However, the cruel reality is that the lack of effective cerebral antidotes for treatment of NA poisoning. There is an urgent requirement for the large-scale evaluation and screening of antidotes. An effective NA antidote should include two characteristics: a) to permeate the blood-brain barrier (BBB); 2) to reactivate the inhibited AChE in brain. Existing methods for evaluating reactivators in vitro can only examine the reactivation effect, while the current Transwell model can only evaluate the drug penetration performance for crossing the barrier. In this work, brain microvascular endothelial cells (RBMECs) were inoculated to establish a Transwell model. AChE, NAs and antidotes of reactivators were added into the different chambers to simulate central poisoning and peripheral drug administration. This method can evaluate the reactivation ability and brain penetration ability of compounds at same time, which is a rapidly and accurately way for drug preliminary screening. In addition to small-molecule drugs, a liposomal nanoantidote loaded with the reactivator Asoxime chloride (HI-6)was prepared. This nanoantidote show high reactivation rate against the NA (sarin), evaluated by both this modified model in vitro and animal test, gaining the consistence results.