Novel delivery of phytochemicals for sustainable crop protection

由于对当前杀虫剂的抗性的进化，迫切需要用于管理昆虫害虫的新解决方案。虫害每年给巴西经济造成177亿美元的损失。我们的项目侧重于纳米技术和金属配位络合物的开发和生物活性测试，作为生物活性植物化学品的新型递送机制，为作物保护提供新的选择。通过使用防御性非宿主植物化学物质，在近交作物的代谢组之外，我们可以提供作物害虫没有进化的植物化学物质。英国和巴西的合作提供了一个理想的机会，分享专业知识，加强这一新的和有前途的研究领域。第一阶段（泵启动）项目已经成功地表明，纳米制剂和植物化学品的复合可以解决低溶解度问题，提高释放寿命和减轻植物毒性，这三个主要问题阻碍了植物杀虫剂的发展。此外，我们的早期（概念验证）植物化学处理具有良好的功效，导致困扰巴西农业的四种主要杀虫剂抗性害虫物种（粉虱，烟粉虱;秋粘虫，草地贪夜蛾;西方花蓟马，花蓟马和桃-马铃薯蚜虫，桃蚜）死亡率> 80%。处理还显示出强烈和显著地抑制蚜虫繁殖（接近完全关闭）并且具有高度显著的驱避活性。第一阶段在基尔大学（英国）的生物学家和圣卡洛斯卡洛斯联邦大学（巴西UFSCar）的化学家之间建立了新的合作关系，通过纳入圣保罗州立大学（巴西UNESP）的作物保护专业知识，进一步加强了合作关系。该项目得益于Keele Nanoceutics的专业知识，使医学研究中的低成本纳米技术能够转化为农业领域。因此，第一阶段的投资为未来的研究奠定了坚实的基础。第二阶段项目将利用第一阶段建立的合作关系，开发新的商业可行的植物化学处理方法。将举办研讨会和互访，使研究小组能够分享专业知识并共同工作。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）使用纳米制剂和络合技术开发和优化植物化学物质的递送。处理将从叶盘扩大到整个植物，详细研究两种有前途的施用途径：可喷雾制剂和通过根灌处理的系统吸收。2)测试制剂对经济上重要的巴西作物害虫靶标的生物活性。抗生素，拒食和驱避活性将使用我们已经开发的四个物种的既定方法进行测试。3)环境和目标特异性评估。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，以便为随后的治疗商业化提供理由。将测量新的生物可降解制剂的分解。非目标效应将通过哺乳动物细胞系、卵寄生蜂赤眼蜂（Trichogramma pretiosum）（一种有益的天敌）和蜜蜂（Apis mellifera）进行评估。我们已经证明了该项目所涉及的学科之间的交叉受精，使农业能够通过使用化学和医学领域已经开发的方法来发展。我们的假设是，我们的新型制剂可以提供一种用于作物保护的“外包”手段，即来自作物害虫尚未进化并因此易受其影响的植物的防御性植物化学物质。第二阶段项目有相当大的潜力产生急需的新工具来管理作物害虫。

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.