Biocompatible Nano-Cocrystal Engineering for Targeted Herbicide Delivery: Enhancing Efficacy through Stimuli-Responsive Release and Reduced Environmental Losses.

In addressing the critical challenges posed by the misuse and inefficiency of traditional pesticides, we introduce a Nano-Cocrystal material composed of the herbicide clopyralid and coformer phenazine. Developed through synergistic supramolecular self-assembly and mechanochemical nanotechnology, this Nano-Cocrystal significantly enhances pesticide performance. It exhibits a marked improvement in stability, with reductions in hygroscopicity and volatility by approximately 38%. Moreover, it intelligently modulates release according to environmental factors, such as temperature, pH, and soil inorganic salts, demonstrating decreased solubility by up to four times and improved wettability and adhesion on leaf surfaces. Importantly, the herbicidal activity surpasses that of pure clopyralid, increasing suppression rates of Medicago sativa L. and Oxalis corniculata L. by up to 27% at the highest dosage. This Nano-Cocrystal also shows enhanced crop safety and reduced genotoxicity compared to conventional formulations. Offering a blend of simplicity, cost-effectiveness, and robust stability, our findings contribute a sustainable solution to agricultural practices, favoring the safety of nontarget organisms.

Cocrystal engineering for sustained release of dicamba: Mitigating secondary drift and reducing leaching.

The off-target effects of herbicides present significant challenges in agricultural practices, posing serious threats to both ecological systems and human health. Dicamba, one of the most widely used herbicides, is particularly problematic due to its high volatility and water solubility, which can lead to rapid environmental dispersal, non-target toxicity, and groundwater contamination. To mitigate these issues, we synthesized a novel cocrystal of dicamba and phenazine (DCB-PHE cocrystal) through a combination of theoretical prediction and mechanochemical screening. The DCB-PHE cocrystal was characterized using single-crystal and powder X-ray diffraction, Fourier-transform infrared spectroscopy (FT-IR), and thermal analysis. Compared to pure dicamba, the DCB-PHE cocrystal exhibited a substantial reduction in volatility by 59 % and a decrease in equilibrium solubility by up to 5.4 times across various temperatures (15 °C, 25 °C, 35 °C). Additionally, the dissolution rates were significantly lowered by over 94 %. Leaching experiments demonstrated that the DCB-PHE cocrystal reduced total leachate by 4.9 % and delayed percolation. In greenhouse trials, the DCB-PHE cocrystal caused less damage to exposed soy plants and enhanced herbicidal activity against target weeds, with fresh weight reduction of chicory and ryegrass by 32 % and 28 %, respectively, at the highest dosage. Furthermore, safety assays confirmed that the DCB-PHE cocrystal's safety profile was comparable to that of dicamba in terms of its impact on wheat, and it did not exhibit increased genotoxicity to broad beans. These findings suggest that the DCB-PHE cocrystal is a promising candidate for reducing the environmental impacts of dicamba while maintaining its herbicidal efficacy.

Pursuing Green and Efficient Agriculture from Molecular Assembly: A Review of Solid-State Forms on Agrochemicals.

Achieving rapid global agricultural development while maintaining ecological harmony is a major challenge of the new millennium. Meeting this challenge requires the development of efficient and environmentally friendly agrochemicals, including pesticides and fertilizers. Molecular assembly, as a promising strategy, has garnered significant attention in recent years for the development of advanced solid-state forms of agrochemicals. In this review, we present the potential and recent advancements of solid-state forms, such as polymorphs, cocrystals/salts, solvates, inclusion compounds, and the amorphous state, for the production of high-efficiency and low-polluting agrochemical products. We provide an overview of the concepts and preparation methods of these solid-state forms, followed by an exploration of their applications in sustainable agriculture. Specifically, we highlight their value in enhancing pesticide solubility, enabling controlled release of chemical fertilizers, and reducing off-target risks. Lastly, we discuss the challenges and prospects associated with the utilization of solid-state forms for the advancement of environmentally friendly and efficient agriculture.

Pedunculoside inhibits epithelial-mesenchymal transition and overcomes Gefitinib-resistant non-small cell lung cancer through regulating MAPK and Nrf2 pathways.

BACKGROUND: Lung cancer is the primary cause of cancer-related mortality worldwide owing to its strong metastatic ability. EGFR-TKI (Gefitinib) has demonstrated efficacy in metastatic lung cancer therapy, but most patients ultimately develop resistance to Gefitinib, leading to a poor prognosis. Pedunculoside (PE), a triterpene saponin extracted from Ilex rotunda Thunb., has shown anti-inflammatory, lipid-lowering and anti-tumor effects. Nevertheless, the therapeutic effect and potential mechanisms of PE on NSCLC treatment are unclear. PURPOSE: To investigate the inhibitory effect and prospective mechanisms of PE on NSCLC metastases and Gefitinib-resistant NSCLC. METHODS: In vitro, A549/GR cells were established by Gefitinib persistent induction of A549 cells with a low dose and shock with a high dose. The cell migratory ability was measured using wound healing and Transwell assays. Additionally, EMT-related Markers or ROS production were assessed by RT-qPCR, immunofluorescence, Western blotting, and flow cytometry assays in A549/GR and TGF-ß1-induced A549 cells. In vivo, B16-F10 cells were intravenously injected into mice, and the effect of PE on tumor metastases were determined using hematoxylin-eosin staining, Caliper IVIS Lumina, DCFH2-DA staining, and western blotting assays. RESULTS: PE reversed TGF-ß1-induced EMT by downregulating EMT-related protein expression through MAPK and Nrf2 pathways, decreasing ROS production, and inhibiting cell migration and invasion ability. Moreover, PE treatment enabled A549/GR cells to retrieve the sensitivity to Gefitinib and mitigate the biological characteristics of EMT. PE also significantly inhibited lung metastasis in mice by reversing EMT proteins expression, decreasing ROS production, and inhibiting MAPK and Nrf2 pathways. CONCLUSIONS: Collectively, this research presents a novel finding that PE can reverse NSCLC metastasis and improve Gefitinib sensitivity in Gefitinib-resistant NSCLC through the MAPK and Nrf2 pathways, subsequently suppressing lung metastasis in B16-F10 lung metastatic mice model. Our findings indicate that PE is a potential agent for inhibiting metastasis and improving Gefitinib resistance in NSCLC.

Salts of 2-hydroxybenzylamine with improvements on solubility and stability: Virtual and experimental screening.

2-Hydroxybenzylamine (2-HOBA) is a drug used to effectively treat oxidative stress. To improve its aqueous solubility and thermal stability, salt screening and synthesis was carried out. The conductor-like screening model for the real solvents model (COSMO-RS) was applied to virtual screening of coformers among 200 commonly used candidates for salification of 2-HOBA. As a result, 40 hit compounds were subjected to experimental liquid-assisted grinding (LAG) with 2-HOBA, then 21 systems were characterized as new solid phases by PXRD. Nine multicomponent single crystals of 2-HOBA with succinic acid, p-aminobenzoic acid, p-nitrobenzoic acid, o-nitrobenzoic acid, p-toluic acid, 2,3-dihydroxybenzoic acid, 3,4-dihydroxybenzoic acid, p-nitrophenol, and 5-hydroxyisophthalic acid were obtained and characterized by single-crystal X-ray diffraction, powder X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. All of them were salts and exhibited higher decomposition temperatures compared with pure 2-HOBA. The apparent aqueous solubility of three new salts, i.e., those with succinic acid, p-aminobenzoic acid, and p-nitrophenol were higher than the equilibrium solubility of 2-HOBA. The accelerated stability test indicated that all salts show excellent stability under conditions (40 °C and 75% RH) for 4 weeks. Overall, this work introduced a protocol that combined the virtual screening tool based on the COSMO-RS model and the experimental LAG method to screen new salts for a target compound. The feasibility of this protocol was confirmed in the case of 2-HOBA whose new salts were successfully obtained and represented an improvement for aqueous solubility and thermal stability.