{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:56:36Z","timestamp":1791388596048,"version":"4.3.3"},"reference-count":50,"publisher":"American Chemical Society (ACS)","issue":"39","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"name":"Shanghai Agricultural Science and Technology Innovation Project","award":["T20252013"],"award-info":[{"award-number":["T20252013"]}]},{"name":"National Basic Research Program of China (973 Program)","award":["2022YFD1700403"],"award-info":[{"award-number":["2022YFD1700403"]}]},{"name":"National Basic Research Program of China (973 Program)","award":["2023YFD1700303"],"award-info":[{"award-number":["2023YFD1700303"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Botrytis cinerea (B. cinerea) causes severe agricultural losses. RNA interference (RNAi) offers precise control but is limited by dsRNA instability and inefficient delivery. Here, dsRNA targeting an ergosterol biosynthesis gene (dsERG) and berberine (BBR) self-assembled into carrier-free nanocomplexes (NCsdsERG-BBR) via microfluidics. The nanocomplexes showed efficient foliar and spore uptake and strongly inhibited spore germination and hyphal growth. Exogenous ergosterol fully rescued the dsERG-induced phenotype but only partially rescued NCsdsERG-BBR, confirming ergosterol biosynthesis inhibition by dsERG and an additional antifungal contribution from BBR. In a grape protective assay, the Bliss-predicted additive inhibition was calculated to be 80.0%, whereas NCsdsERG-BBR achieved 96.9% inhibition, demonstrating a synergistic effect under this condition. These findings indicate that the enhanced antifungal performance of NCsdsERG-BBR arises from improved delivery, BBR activity, and synergy, providing a scalable, solvent-free platform for sustainable crop protection.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c00490","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:02:13Z","timestamp":1790053333000},"page":"30491-30501","source":"Crossref","is-referenced-by-count":0,"title":["Microfluidic-Directed Self-Assembly of dsRNA-Fungicide\nNanocomplexes toward Synergistically Enhanced Disease Control"],"prefix":"10.1021","volume":"74","author":[{"given":"Ting","family":"Li","sequence":"first","affiliation":[{"name":"East China University of Science and Technology , , 130 Meilong Road , ,","place":["Shanghai, P.R. China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqin","family":"Wu","sequence":"additional","affiliation":[{"name":"East China University of Science and Technology , , 130 Meilong Road , ,","place":["Shanghai, P.R. China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4628-370X","authenticated-orcid":true,"given":"Shuning","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Plant Protection, Chinese Academy of Agricultural Sciences , , ,","place":["Beijing, China, 100193"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengyu","family":"Lei","sequence":"additional","affiliation":[{"name":"Institute of Plant Protection, Chinese Academy of Agricultural Sciences , , ,","place":["Beijing, China, 100193"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4946-4722","authenticated-orcid":true,"given":"Yufang","family":"Xu","sequence":"additional","affiliation":[{"name":"East China University of Science and Technology , , 130 Meilong Road , ,","place":["Shanghai, P.R. China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6777-0673","authenticated-orcid":true,"given":"Xuhong","family":"Qian","sequence":"additional","affiliation":[{"name":"East China University of Science and Technology , , 130 Meilong Road , ,","place":["Shanghai, P.R. China, 200237"]},{"name":"East China University of Science and Technology , , ,","place":["Shanghai, China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5201-0468","authenticated-orcid":true,"given":"Weiping","family":"Zhu","sequence":"additional","affiliation":[{"name":"East China University of Science and Technology , , 130 Meilong Road , ,","place":["Shanghai, P.R. China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9595-0206","authenticated-orcid":true,"given":"Yangyang","family":"Yang","sequence":"additional","affiliation":[{"name":"East China University of Science and Technology , , 130 Meilong Road , ,","place":["Shanghai, P.R. China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"issue":"6","key":"2026100711065841600_cit1","doi-asserted-by":"publisher","first-page":"2072","DOI":"10.3390\/ijms21062072","article-title":"RNAi-Based Biofungicides as a Promising next-Generation\nStrategy for Controlling Devastating Gray Mold Diseases","volume":"21","author":"Islam","year":"2020","journal-title":"Int. J. Mol. Sci."},{"issue":"6","key":"2026100711065841600_cit2","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1111\/mpp.12794","article-title":"Grey Mould\nof Strawberry, a Devastating Disease Caused by the Ubiquitous Necrotrophic\nFungal Pathogen Botrytis Cinerea","volume":"20","author":"Petrasch","year":"2019","journal-title":"Mol. Plant\nPathol."},{"key":"2026100711065841600_cit3","unstructured":"Fungicide Resistance Action Committee (FRAC).\n          \n          FRAC\nPathogen Risk List; Fungicide Resistance Action Committee, 2019. https:\/\/www.frac.info\/media\/qluf3unn\/frac-pathogen-list-2019.pdf."},{"key":"2026100711065841600_cit4","doi-asserted-by":"publisher","first-page":"140211","DOI":"10.1016\/j.ijbiomac.2025.140211","article-title":"Chitosan- and Sodium Alginate-Coated\nDendritic Mesoporous Organosilica\nNanoparticles Improve Pesticide Adhesion on Leaves and Enable Dual-Stimulus-Responsive\nRelease","volume":"299","author":"Lin","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"issue":"27","key":"2026100711065841600_cit5","doi-asserted-by":"publisher","first-page":"32295","DOI":"10.1021\/acsami.1c08582","article-title":"Supramolecular\nNanoplatform Based\non Mesoporous Silica Nanocarriers and Pillararene Nanogates for Fungus\nControl","volume":"13","author":"Wang","year":"2021","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"2026100711065841600_cit6","doi-asserted-by":"publisher","first-page":"9","DOI":"10.3389\/fmicb.2018.00059","article-title":"Impact of Chemical\nand Biological Fungicides Applied to Grapevine on Grape Biofilm, Must,\nand Wine Microbial Diversity","volume":"9","author":"Escribano-Viana","year":"2018","journal-title":"Front. Microbiol."},{"issue":"1","key":"2026100711065841600_cit7","doi-asserted-by":"publisher","first-page":"7989","DOI":"10.1038\/s41598-022-11533-w","article-title":"A Novel Approach to Control Botrytis Cinerea Fungal\nInfections: Uptake and Biological Activity of Antifungals Encapsulated\nin Nanoparticle Based Vectors","volume":"12","author":"De Angelis","year":"2022","journal-title":"Sci. Rep."},{"key":"2026100711065841600_cit8","doi-asserted-by":"publisher","first-page":"137778","DOI":"10.1016\/j.scitotenv.2020.137778","article-title":"Nanotechnology\nin Agriculture: Current Status, Challenges and Future Opportunities","volume":"721","author":"Usman","year":"2020","journal-title":"Sci. Total Environ."},{"issue":"18","key":"2026100711065841600_cit9","doi-asserted-by":"publisher","first-page":"10778","DOI":"10.1021\/acs.jafc.4c13212","article-title":"Spray-Induced Gene\nSilencing for Postharvest Protection: dsRNA Stability and Insecticidal\nEfficacy","volume":"73","author":"Chen","year":"2025","journal-title":"J. Agric. Food Chem."},{"key":"2026100711065841600_cit10","doi-asserted-by":"publisher","first-page":"16","DOI":"10.3389\/fpls.2025.1527944","article-title":"Spray-Induced\nGene Silencing for Crop Protection: Recent Advances and Emerging Trends","volume":"16","author":"Chen","year":"2025","journal-title":"Front. 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Nanobiotechnol."},{"key":"2026100711065841600_cit13","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1146\/annurev-ento-011019-025224","article-title":"Mechanisms, Applications,\nand Challenges of Insect\nRNA Interference","volume":"65","author":"Zhu","year":"2020","journal-title":"Annu. Rev. Entomol."},{"issue":"7","key":"2026100711065841600_cit14","doi-asserted-by":"publisher","first-page":"483","DOI":"10.3390\/jof10070483","article-title":"Development of an RNA\nNanostructure for Effective Botrytis Cinerea Control through Spray-Induced\nGene Silencing without an Extra Nanocarrier","volume":"10","author":"Wu","year":"2024","journal-title":"J. Fungi."},{"issue":"5","key":"2026100711065841600_cit15","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1111\/j.1365-2583.2010.01029.x","article-title":"Chitosan\/Double-Stranded RNA Nanoparticle-Mediated\nRNA Interference to Silence Chitin Synthase Genes through Larval Feeding\nin the African Malaria Mosquito (Anopheles Gambiae)","volume":"19","author":"Zhang","year":"2010","journal-title":"Insect Mol. Biol."},{"issue":"1","key":"2026100711065841600_cit16","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s42483-023-00157-1","article-title":"Nanoparticle\nCarriers Enhance RNA Stability and Uptake Efficiency\nand Prolong the Protection against Rhizoctonia Solani","volume":"5","author":"Wang","year":"2023","journal-title":"Phytopathol. Res."},{"issue":"1","key":"2026100711065841600_cit17","doi-asserted-by":"publisher","first-page":"9158","DOI":"10.1038\/s41467-024-53468-y","article-title":"The Role of Polymers\nin Enabling\nRNAi-Based Technology for Sustainable Pest Management","volume":"15","author":"Quilez-Molina","year":"2024","journal-title":"Nat. Commun."},{"issue":"2","key":"2026100711065841600_cit18","doi-asserted-by":"publisher","first-page":"16207","DOI":"10.1038\/nplants.2016.207","article-title":"Clay Nanosheets for Topical Delivery\nof RNAi for Sustained Protection\nagainst Plant Viruses","volume":"3","author":"Mitter","year":"2017","journal-title":"Nat. Plants"},{"key":"2026100711065841600_cit19","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.jare.2024.01.031","article-title":"Self-Assembled Co-Delivery Nanoplatform for Increasing the Broad-Spectrum\nSusceptibility of Fall Armyworm toward Insecticides","volume":"67","author":"Yan","year":"2025","journal-title":"J. Adv. 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Eng.\nJ."},{"key":"2026100711065841600_cit24","doi-asserted-by":"publisher","first-page":"173821","DOI":"10.1016\/j.scitotenv.2024.173821","article-title":"Carrier-Free\nSelf-Assembled Nanoparticles Based on Prochloraz and Fenhexamid for\nReducing Toxicity to Aquatic Organism","volume":"943","author":"Zhou","year":"2024","journal-title":"Sci.\nTotal Environ."},{"issue":"8","key":"2026100711065841600_cit25","doi-asserted-by":"publisher","first-page":"4758","DOI":"10.1002\/ps.8838","article-title":"Carrier-Free Co-Delivery Nanosystem\nBased on Prothioconazole and Pyrimethanil to Enhance Fungicidal Efficacy\nand Reduce Environmental Risks","volume":"81","author":"Liu","year":"2025","journal-title":"Pest Manage.\nSci."},{"key":"2026100711065841600_cit26","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.ejphar.2015.05.068","article-title":"Current Knowledge and Pharmacological\nProfile of Berberine: An Update","volume":"761","author":"Kumar","year":"2015","journal-title":"Eur. J. Pharmacol."},{"issue":"6","key":"2026100711065841600_cit27","doi-asserted-by":"publisher","first-page":"6770","DOI":"10.1021\/acsnano.9b01346","article-title":"Natural Berberine-Based\nChinese Herb Medicine Assembled Nanostructures\nwith Modified Antibacterial Application","volume":"13","author":"Li","year":"2019","journal-title":"ACS\nNano"},{"key":"2026100711065841600_cit28","doi-asserted-by":"publisher","first-page":"8621","DOI":"10.2147\/IJN.S469350","article-title":"Transforming Cancer Treatment with Nanotechnology: The Role of Berberine\nas a Star Natural Compound","volume":"19","author":"Sun","year":"2024","journal-title":"Int. J. Nanomed."},{"issue":"14","key":"2026100711065841600_cit29","doi-asserted-by":"publisher","first-page":"7716","DOI":"10.1021\/acs.jafc.3c08858","article-title":"Antifungal Activity\nand Putative Mechanism of HWY-289,\na Semisynthetic Protoberberine Derivative, against Botrytis Cinerea","volume":"72","author":"An","year":"2024","journal-title":"J. Agric. Food Chem."},{"issue":"9","key":"2026100711065841600_cit30","doi-asserted-by":"publisher","first-page":"1784","DOI":"10.1016\/j.apsb.2019.12.014","article-title":"Self-Assembled Natural\nPhytochemicals for Synergistically Antibacterial\nApplication from the Enlightenment of Traditional Chinese Medicine\nCombination","volume":"10","author":"Tian","year":"2020","journal-title":"Acta Pharm. Sin. B"},{"issue":"7","key":"2026100711065841600_cit31","doi-asserted-by":"publisher","first-page":"1782","DOI":"10.3390\/pharmaceutics15071782","article-title":"Fabrication of Co-Assembly\nfrom Berberine and Tannic Acid for Multidrug-Resistant Bacteria Infection\nTreatment","volume":"15","author":"Zheng","year":"2023","journal-title":"Pharmaceutics"},{"issue":"4","key":"2026100711065841600_cit32","doi-asserted-by":"publisher","first-page":"742","DOI":"10.3390\/molecules24040742","article-title":"Inhibitory\nEffects of Berberine Hydrochloride on Trichophyton\nMentagrophytes and the Underlying Mechanisms","volume":"24","author":"Xiao","year":"2019","journal-title":"Molecules"},{"issue":"6","key":"2026100711065841600_cit33","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1002\/med.20202","article-title":"Therapeutic Potential of Nucleic Acid-Binding Isoquinoline\nAlkaloids: Binding Aspects and Implications for Drug Design","volume":"31","author":"Bhadra","year":"2011","journal-title":"Med. Res. Rev."},{"issue":"3","key":"2026100711065841600_cit34","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1039\/D1LC00812A","article-title":"Microfluidic Technologies for Nanoparticle\nFormation","volume":"22","author":"Tian","year":"2022","journal-title":"Lab Chip"},{"issue":"25","key":"2026100711065841600_cit35","doi-asserted-by":"publisher","first-page":"12430","DOI":"10.1039\/C5NR07964K","article-title":"Microfluidics-Mediated\nAssembly of Functional Nanoparticles\nfor Cancer-Related Pharmaceutical Applications","volume":"8","author":"Feng","year":"2016","journal-title":"Nanoscale"},{"key":"2026100711065841600_cit36","doi-asserted-by":"publisher","first-page":"120826","DOI":"10.1016\/j.biomaterials.2021.120826","article-title":"Microfluidic Formulation of Nanoparticles\nfor Biomedical Applications","volume":"274","author":"Shepherd","year":"2021","journal-title":"Biomaterials"},{"issue":"36","key":"2026100711065841600_cit37","doi-asserted-by":"publisher","first-page":"2106580","DOI":"10.1002\/smll.202106580","article-title":"Microfluidic Nanoparticles for Drug\nDelivery","volume":"18","author":"Liu","year":"2022","journal-title":"Small"},{"issue":"3","key":"2026100711065841600_cit38","doi-asserted-by":"publisher","first-page":"2365","DOI":"10.1021\/acsnano.7b07635","article-title":"Reconfigurable Microfluidic\nDroplets Stabilized by Nanoparticle Surfactants","volume":"12","author":"Toor","year":"2018","journal-title":"ACS Nano"},{"key":"2026100711065841600_cit39","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.addr.2018.04.001","article-title":"Microfluidics\nin Nanoparticle Drug Delivery; From Synthesis to Pre-Clinical Screening","volume":"128","author":"Ahn","year":"2018","journal-title":"Adv. Drug Delivery Rev."},{"key":"2026100711065841600_cit40","doi-asserted-by":"publisher","first-page":"121088","DOI":"10.1016\/j.ijpharm.2021.121088","article-title":"Microfluidic Assembly\nof Small-Molecule Prodrug Cocktail Nanoparticles with High Reproducibility\nfor Synergistic Combination of Cancer Therapy","volume":"608","author":"Li","year":"2021","journal-title":"Int. J. Pharm."},{"issue":"13","key":"2026100711065841600_cit41","doi-asserted-by":"publisher","first-page":"2209672","DOI":"10.1002\/adma.202209672","article-title":"Microfluidics-Enabled Serial Assembly of Lipid-siRNA-Sorafenib\nNanoparticles for Synergetic Hepatocellular Carcinoma Therapy","volume":"35","author":"Chen","year":"2023","journal-title":"Adv. Mater."},{"issue":"22","key":"2026100711065841600_cit42","doi-asserted-by":"publisher","first-page":"12508","DOI":"10.1021\/acs.jafc.4c03307","article-title":"Microfluidic-Based\ndsRNA Delivery Nanoplatform for Efficient Spodoptera Exigua Control","volume":"72","author":"Xie","year":"2024","journal-title":"J. Agric. Food Chem."},{"issue":"1","key":"2026100711065841600_cit43","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.postharvbio.2011.02.005","article-title":"Activity of\nExtracts from Wild Edible Herbs against Postharvest Fungal Diseases\nof Fruit and Vegetables","volume":"61","author":"Gatto","year":"2011","journal-title":"Postharvest Biol. Technol."},{"issue":"4","key":"2026100711065841600_cit44","doi-asserted-by":"publisher","first-page":"558","DOI":"10.3390\/microorganisms8040558","article-title":"Harvesting Mango Fruit\nwith a Short Stem-End Altered Endophytic Microbiome and Reduce Stem-End\nRot","volume":"8","author":"Galsurker","year":"2020","journal-title":"Microorganisms"},{"issue":"1","key":"2026100711065841600_cit45","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1111\/pbi.13708","article-title":"Double-Stranded\nRNA Targeting Fungal Ergosterol Biosynthesis Pathway Controls Botrytis\nCinerea and Postharvest Grey Mould","volume":"20","author":"Duanis-Assaf","year":"2022","journal-title":"Plant Biotechnol.\nJ."},{"issue":"1","key":"2026100711065841600_cit46","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.micpath.2009.10.001","article-title":"Evolution of Ergosterol\nBiosynthesis Inhibitors as Fungicidal against Candida","volume":"48","author":"Ahmad","year":"2010","journal-title":"Microb. Pathog."},{"issue":"12","key":"2026100711065841600_cit47","doi-asserted-by":"publisher","first-page":"2708","DOI":"10.1128\/AAC.39.12.2708","article-title":"Deletion of the Candida Glabrata\nERG3 and ERG11 Genes: Effect on Cell Viability, Cell Growth, Sterol\nComposition, and Antifungal Susceptibility","volume":"39","author":"Geber","year":"1995","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026100711065841600_cit48","doi-asserted-by":"publisher","first-page":"16151","DOI":"10.1038\/nplants.2016.151","article-title":"Bidirectional Cross-Kingdom\nRNAi and Fungal Uptake of External RNAs\nConfer Plant Protection","volume":"2","author":"Wang","year":"2016","journal-title":"Nat. Plants"},{"issue":"13","key":"2026100711065841600_cit49","doi-asserted-by":"publisher","first-page":"5671","DOI":"10.1021\/acs.nanolett.1c01353","article-title":"Scalable mRNA and\nsiRNA Lipid Nanoparticle Production\nUsing a Parallelized Microfluidic Device","volume":"21","author":"Shepherd","year":"2021","journal-title":"Nano\nLett."},{"issue":"10","key":"2026100711065841600_cit50","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1038\/nnano.2012.168","article-title":"Microfluidic\nTechnologies\nfor Accelerating the Clinical Translation of Nanoparticles","volume":"7","author":"Valencia","year":"2012","journal-title":"Nat. Nanotechnol."}],"container-title":["Journal of Agricultural and Food Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jafc.6c00490","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/39\/30491\/68589564\/acs.jafc.6c00490.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/39\/30491\/68589564\/acs.jafc.6c00490.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:32:40Z","timestamp":1791387160000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jafcau\/article\/74\/39\/30491\/5434820\/Microfluidic-Directed-Self-Assembly-of-dsRNA"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,22]]},"references-count":50,"journal-issue":{"issue":"39","published-online":{"date-parts":[[2026,9,22]]},"published-print":{"date-parts":[[2026,10,7]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jafc.6c00490","relation":{},"ISSN":["0021-8561","1520-5118"],"issn-type":[{"value":"0021-8561","type":"print"},{"value":"1520-5118","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,22]]}}}