Chemotherapy drugs derived nanoparticles encapsulating mRNA encoding tumor suppressor proteins to treat triple-negative breast cancer

Triple-negative breast cancer (TNBC) is one type of the most aggressive breast cancers with poor prognosis. It is of great urgency to develop new therapeutics for treating TNBC. Based on current treatment guideline and genetic information of TNBC, a combinational therapy platform integrating chemotherapy drugs and mRNA encoding tumor suppressor proteins may become an efficacious strategy. In this study, we developed paclitaxel amino lipid (PAL) derived nanoparticles (NPs) to incorporate both chemotherapy drugs and P53 mRNA. The PAL P53 mRNA NPs showed superior properties compared to Abraxane^® and Lipusu^® used in the clinic including high paclitaxel loading capacity (24 wt.%, calculated by paclitaxel in PAL), PAL encapsulation efficiency (94.7% ± 6.8%) and mRNA encapsulation efficiency (88.7% ± 0.7%). Meanwhile, these NPs displayed synergetic cytotoxicity of paclitaxel and P53 mRNA in cultured TNBC cells. More importantly, we demonstrated in vivo anti-tumor efficacy of PAL P53 mRNA NPs in an orthotopic TNBC mouse model. Overall, these chemotherapy drugs derived mRNA NPs provide a new platform to integrate chemotherapy and personalized medicine using tumor genetic information, and therefore represent a promising approach for TNBC treatment.

     

A Versatile Theranostic Nanoemulsion for Architecture‐Dependent Multimodal Imaging and Dually Augmented Photodynamic Therapy

To design a clinically translatable nanomedicine for photodynamic theranostics, the ingredients should be carefully considered. A high content of nanocarriers may cause extra toxicity in metabolism, and multiple theranostic agents would complicate the preparation process. These issues would be of less concern if the nanocarrier itself has most of the theranostic functions. In this work, a poly(ethylene glycol)‐boron dipyrromethene amphiphile (PEG‐F₅₄‐BODIPY) with 54 fluorine‐19 (¹⁹F) is synthesized and employed to emulsify perfluorohexane (PFH) into a theranostic nanoemulsion (PFH@PEG‐F₅₄‐BODIPY). The as‐prepared PFH@PEG‐F₅₄‐BODIPY can perform architecture‐dependent fluorescence/photoacoustic/¹⁹F magnetic resonance multimodal imaging, providing more information about the in vivo structure evolution of nanomedicine. Importantly, this nanoemulsion significantly enhances the therapeutic effect of BODIPY through both the high oxygen dissolving capability and less self‐quenching of BODIPY molecules. More interestingly, PFH@PEG‐F₅₄‐BODIPY shows high level of tumor accumulation and long tumor retention time, allowing a repeated light irradiation after a single‐dose intravenous injection. The “all‐in‐one” photodynamic theranostic nanoemulsion has simple composition, remarkable theranostic efficacy, and novel treatment pattern, and thus presents an intriguing avenue to developing clinically translatable theranostic agents.     

Distributed H∞ consensus control for nonlinear multi-agent systems under switching topologies via relative output feedback

Neural Computing and Applications - For a class of nonlinear multi-agent systems under switching topologies with disturbances, we propose a distributed H∞ consensus control protocol based on...     

Un-jamming due to energetic instability: statics to dynamics

Granular Matter - A method to identify the parameters of rolling resistance between particles in the discrete element method is proposed in this paper. Experiments revealed that a free rolling...     

The effect of optimized carbon source on the synthesis and composition of exopolysaccharides produced by Lactobacillus paracasei

This study aimed to predict the optimal carbon source for higher production of exopolysaccharides (EPS) by Lactobacillus paracasei TD 062, and to evaluate the effect of this carbon source on the production and monosaccharide composition of EPS. We evaluated the EPS production capacity of 20 strains of L. paracasei under the same conditions. We further investigated L. paracasei TD 062, which showed the highest EPS-producing activity (0.609 g/L), by examining the associated biosynthesis pathways for EPS. Genomics revealed that fructose, mannose, trehalose, glucose, galactose, and lactose were carbon sources that L. paracasei TD 062 could use to produce EPS. We identified an EPS synthesis gene cluster that could participate in transport, export, and sugar chain synthesis, and generate 6 sugar nucleotides. Experimental results showed that the sugar content of the EPS produced using fermentation with the optimized carbon source (fructose, mannose, trehalose, glucose, galactose, and lactose) increased by 115%. Furthermore, use of the optimized carbon source changed the monosaccharide content of the associated EPS. The results of enzyme activity measurements showed significant increases in the activity of 2 key enzymes involved in the glycoside synthesis pathway. Our study revealed that optimizing the carbon source provided for fermentation not only increased the production of EPS, but also affected the composition of the monosaccharides by increasing enzyme activity in the underlying synthesis pathways, suggesting an important role for carbon source in the production of EPS by L. paracasei TD 062.     

Rapid screening of DON contamination in whole wheat meals by Vis/NIR spectroscopy and computer vision coupling technology

This work intends to develop an online experimental system for screening of deoxynivalenol (DON) contamination in whole wheat meals by visible/near-infrared (Vis/NIR) spectroscopy and computer vision coupling technology. Spectral and image information of samples with various DON levels was collected at speed of 0.15 m s⁻¹ on a conveyor belt. The two-type data were then integrated and subjected to chemometric analysis. Discriminant analysis showed that samples could be classified by setting 1000 μg kg⁻¹ as the cut-off value. The best correct classified rate obtained in prediction was 93.55% based on fusion of spectral and image features, with reduced prediction uncertainty as compared to single feature. However, quantification of DON by quantitative analysis was not successful due to poor model performance. These results indicate that, although not accurate enough to provide conclusive result, this coupling technology could be adopted for rapid screening of DON contamination in cereals and feeds during processing.     

Microwave synthesis of worm-like SiC nanowires for thin electromagnetic wave absorbing materials

Thin thickness is always the pursuit of excellent electromagnetic wave absorbing materials. Herein, SiC nanowires with worm-like morphology were synthesized by microwave heating the mixture of expanded graphite and silica. The worm-like SiC nanowires exhibit an excellent microwave absorption ability at a thin thickness. With the filling ratio of SiC nanowires increases in the matrix, the dielectric loss and microwave absorbing ability are significantly enhanced; meanwhile the number of absorption peaks is gradually increased, and the absorption peaks also move toward a thinner thickness. When the nanowires filling ratio was 40?wt%, the minimum reflection loss reached down to ?35.2?dB and the effective absorption (RL?<??10?dB) bandwidth was 1.8?GHz?at a thickness of 1.3?mm. The possible growth mechanism of the worm-like SiC nanowires is that the intermediate reaction gas phases, SiO and CO, were confined in the relatively independent tiny pores of expanded graphite. This resulting in an excessive local gas phase pressure, which causes the nanowire growth direction changes randomly.     

Research on the machinability of A-plane sapphire under diamond wire sawing in different sawing directions

Due to its superior mechanical, optical and chemical properties, sapphire (α-Al₂O₃) is widely used in engineering, optics, medicine, and other scientific research fields. The atomic structure of sapphire gives rise to anisotropy in its mechanical properties, which affects the machinability of sapphire materials on different crystal planes. Different cutting directions will affect the wafer economy and surface quality achieved during wire sawing due to this anisotropy. In this study, the machinability of A-plane sapphire was investigated for diamond wire sawing in three different directions, following the C-plane, R-plane and M-plane. The results show that the direction following the M-plane could be the best direction for diamond wire sawing because this direction results in the minimal sawing forces, the lowest specific energy and the smallest volume of material that will need to be removed during subsequent processing. These characteristics correspond to the direction with the highest fracture strength since the material is removed by brittle machining. The force ratio for sawing in the direction of the R-plane is the smallest because this direction is associated with the minimum hardness and the lowest critical load for the transition from plastic to brittle removal of the workpiece material. The 3D height parameters show no obvious pattern among the three sawing directions. The mechanism of material removal is mainly brittle removal, with some plastic removal, and is obviously affected by the crystal orientation.