Novel delivery of phytochemicals for sustainable crop protection

由于对现有杀虫剂的抗性进化，迫切需要新的害虫管理解决方案。害虫每年给巴西经济造成177亿美元的损失。本项目致力于纳米技术和金属配合物作为植物生物活性物质的新型传递机制的开发和生物活性测试，为作物保护提供新的选择。通过使用防御性的非寄主植物化学物质，在自交系作物的代谢组之外，我们可以提供作物害虫没有进化的植物化学物质。英国和巴西的合作为分享专业知识和加强这一新的有前途的研究领域提供了一个理想的机会。第一阶段（泵启动）项目已经成功地表明，纳米配方和络合植物化学物质可以解决低溶解度问题，提高释放寿命和减轻植物毒性；迄今为止，有三个主要问题阻碍了植物杀虫剂的发展。此外，我们的早期（概念证明）植物化学处理具有良好的效果，对困扰巴西农业的四种主要抗杀虫剂害虫（白蝇，烟粉虱，夜粘虫，穗状夜蛾，西花蓟马，西Frankliniella occidentalis和桃马铃薯蚜虫，Myzus persicae）造成了80%的死亡率。处理还显示出强烈和显著地抑制蚜虫繁殖（几乎完全关闭），并具有高度显著的驱避活性。第一阶段在基尔大学（英国）的生物学家和<s:1>奥卡洛斯联邦大学（巴西）的化学家之间建立了新的合作关系，<s:1>圣保罗州立大学（巴西）的作物保护专业知识进一步加强了这一合作。该项目受益于Keele Nanoceutics的专业知识，允许将医学研究中的低成本纳米技术转化为农业领域。因此，第一阶段的投资为未来的研究提供了坚实的基础。第二阶段项目将利用第一阶段建立的合作，朝着产生新的商业上可行的植物化学处理的方向发展。将举办讲习班和交流访问，使研究小组能够分享专业知识并共同努力。我们计划举办三个研讨会：UNESP（2019年6月），Keele（2020年1月）和UFSCar（2021年1月）。实验工作将集中在三个主要领域：1)利用纳米配方和络合技术开发和优化植物化学传递。处理将从叶片扩大到整个植物，并详细研究两种有前途的应用途径：喷雾配方和通过根淋处理的系统吸收。2)测试配方对经济上重要的巴西作物害虫目标的生物活性。抗生素、拒食和驱避活性将使用我们为这四个物种开发的既定方法进行测试。3)环境和靶标特异性评估。我们正在测试的大多数植物化学物质和配方已经被广泛用作食品成分、药物或芳香疗法。然而，我们将获得证据，以便为后续治疗的商业化提供证据。将测量新的生物可降解配方的分解情况。非靶标效应将用哺乳动物细胞系、卵类寄生蜂赤眼蜂（一种有益的天敌）和蜜蜂进行评估。我们已经展示了项目中涉及的学科之间的交叉施肥，允许农业通过使用化学和医学中已经开发的方法来推进。我们的假设是，我们的新配方可以为作物保护提供一种“外包”手段，从作物害虫没有进化的植物中获取防御性植物化学物质，因此容易受到影响。第二阶段项目具有相当大的潜力，可以产生急需的管理作物有害生物的新工具。

New solutions for managing insect pests are urgently needed due to evolution of resistance to current insecticides. Insect pests cause annual losses of US$17.7 billion to the Brazilian economy. Our project focuses on development and bioactivity testing of nanotech and metallic coordination complexes as novel delivery mechanisms for bioactive phytochemcials, to provide new options for crop protection. By using defensive non-host phytochemicals, outside the metabolome of inbred crops, we can deliver phytochemcials that crop pests have not evolved with. UK-Brazil collaboration provides an ideal opportunity to share expertise and strengthen this new and promising area of research.The Stage 1 (pump-priming) project has successfully shown that nanoformulation and complexing of phytochemicals can solve low solubility issues, improve longevity of release and alleviate phytotoxicity; three major issues that have impeded the development of botanical insecticides to date. Furthermore, our early (proof of concept) phytochemical treatments have good efficacy, causing > 80% mortality of four major insecticide resistant pest species that are plaguing Brazilian agriculture (whitefly, Bemisia tabaci; fall armyworm, Spodoptera frugiperda; Western flower thrips, Frankliniella occidentalis, and peach-potato aphid, Myzus persicae). Treatments were also shown to strongly and significantly inhibit aphid reproduction (near complete shutdown) and had highly significant repellent activity. Stage 1 established a new collaboration between Biologists at Keele University (UK) and Chemists at the Federal University of São Carlos (UFSCar, Brazil), which was further strengthened by inclusion of crop protection expertise at São Paulo State University (UNESP, Brazil). The project has benefited from Keele Nanoceutics expertise, allowing low cost nanotech technologies from medical research to be translated into the agricultural field. Investment in Stage 1 has thus provided a solid foundation for future research.The Stage 2 project will use the collaboration established in Stage 1 to move towards generating new commercially viable phytochemical treatments. Workshops and exchange visits will be held to allow research groups to share expertise and work together. We have three workshops planned: UNESP (June 2019), Keele (Jan 2020) and UFSCar (Jan 2021). Experimental work will focus on three main areas: 1) Development and optimisation of phytochemical delivery using nanoformulation and complexing techniques. Treatments will be scaled up from leaf discs to whole plants with detailed investigation of two promising routes for application: sprayable formulations and systemic uptake via root drench treatments. 2) Testing bioactivity of formulations against economically important Brazilian crop pest targets. Antibiotic, antifeedant and repellent activity will be tested for using established methods we have developed for the four species. 3) Environmental and target specificity assessment. Most of the phytochemicals and formulations we are testing are already widely used as food ingredients, in medicine or in aromatherapy. However, we will obtain evidence in order to make the case for subsequent commercialisation of treatments. Breakdown of new biodegradable formulations will be measured. Non-target effects will be assessed with mammalian cell lines, an egg parasitoid wasp Trichogramma pretiosum (a beneficial natural enemy), and the honeybee, Apis mellifera.We have shown cross-fertilisation between the disciplines involved in the project, allowing Agriculture to advance by using approaches already developed in Chemistry and Medicine. Our hypothesis is that our novel formulations could provide a means to "outsource", for crop protection, defensive phytochemicals from plants that crop pests have not evolved with and therefore are susceptible to. The Stage 2 project has considerable potential to generate much needed new tools for managing crop pests.