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Inspired by the modular assembly concept of \u201cLego-bricks\u201d, this study constructed naringin\u2013chlorogenic acid\u2013glucosylrutin carrier-free nanoparticles (NCGN) with high apparent co-assembly efficiency (95.38 \u00b1 0.77%) and loading capacity (32.54 \u00b1 0.47%) through supramolecular self-assembly, leading to 4.6-fold increase in the aqueous solubility of NG. Investigation into the supramolecular self-assembly mechanism revealed that the process was primarily driven by \u03c0\u2013\u03c0 stacking between aromatic rings, with synergistic effects from hydrogen bonding and van der Waals forces. Notably, the release efficiency of NCGN reached 93.4% in simulated solutions, which was predominantly driven by non-Fickian diffusion and skeletal dissolution. The biocompatibility evaluation revealed non-toxicity within the tested concentration range of 100 \u03bcg\/mL, indicating good biocompatibility. In vitro anti-inflammatory experiments showed that NCGN exhibited significantly reduced levels of IL-6 and TNF-\u03b1, demonstrating its potent anti-inflammatory activity.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c07395","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:01:45Z","timestamp":1790092905000},"page":"30802-30816","source":"Crossref","is-referenced-by-count":0,"title":["\u201cLego-Brick\u201d-Style\nSupramolecular Self-Assembly\nfor Naringin\u2013Chlorogenic Acid\u2013Glucosylrutin Carrier-Free\nNanoparticles: Self-Assembly Mechanism, Release Behavior, and Anti-Inflammatory\nActivity"],"prefix":"10.1021","volume":"74","author":[{"given":"Peng","family":"Zhou","sequence":"first","affiliation":[{"name":"Hunan Academy of Agricultural Sciences , , ,","place":["Changsha, China, 410125"]},{"name":"Yuelushan Laboratory , ,","place":["Changsha, Hunan, China, 410125"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XinYao","family":"Wang","sequence":"additional","affiliation":[{"name":"Hunan Academy of Agricultural Sciences , , ,","place":["Changsha, China, 410125"]},{"name":"Hunan Agricultural University , , ,","place":["Changsha, China, 410128"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Guo","sequence":"additional","affiliation":[{"name":"Hunan Academy of Agricultural Sciences , , ,","place":["Changsha, China, 410125"]},{"name":"Zhejiang University , , , ,","place":["Hangzhou, Zhejiang, China, 310058"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shikai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hunan Academy of Agricultural Sciences , , ,","place":["Changsha, China, 410125"]},{"name":"Yuelushan Laboratory , ,","place":["Changsha, Hunan, China, 410125"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xie","sequence":"additional","affiliation":[{"name":"Hunan Academy of Agricultural Sciences , , ,","place":["Changsha, China, 410125"]},{"name":"Hunan University , , , ,","place":["Changsha, Hunan, China, 410082"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wensheng","family":"Li","sequence":"additional","affiliation":[{"name":"Hunan University , , , ,","place":["Changsha, Hunan, China, 410082"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Xiao","sequence":"additional","affiliation":[{"name":"Hunan Academy of Agricultural Sciences , , ,","place":["Changsha, China, 410125"]},{"name":"Yuelushan Laboratory , ,","place":["Changsha, Hunan, China, 410125"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Shan","sequence":"additional","affiliation":[{"name":"Hunan Academy of Agricultural Sciences , , ,","place":["Changsha, China, 410125"]},{"name":"Yuelushan Laboratory , ,","place":["Changsha, Hunan, China, 410125"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2383-0843","authenticated-orcid":true,"given":"Shenghua","family":"Ding","sequence":"additional","affiliation":[{"name":"Hunan Academy of Agricultural Sciences , , ,","place":["Changsha, China, 410125"]},{"name":"Yuelushan Laboratory , ,","place":["Changsha, Hunan, China, 410125"]},{"name":"Hunan Agricultural University , , ,","place":["Changsha, China, 410128"]},{"name":"Hunan University , , , ,","place":["Changsha, Hunan, China, 410082"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"issue":"1","key":"2026100711070023700_cit1","doi-asserted-by":"publisher","first-page":"3991","DOI":"10.1038\/s41467-024-48235-y","article-title":"An integrated\nmulti-omics approach reveals polymethoxylated flavonoid biosynthesis\nin Citrus reticulata cv. Chachiensis","volume":"15","author":"Wen","year":"2024","journal-title":"Nat. Commun."},{"key":"2026100711070023700_cit2","doi-asserted-by":"publisher","first-page":"107871","DOI":"10.1016\/j.phrs.2025.107871","article-title":"Naringenin\/naringin\ntherapeutic effects and the role of intestinal microflora in them","volume":"219","author":"Huang","year":"2025","journal-title":"Pharmacol. Res."},{"key":"2026100711070023700_cit3","doi-asserted-by":"publisher","first-page":"110029","DOI":"10.1016\/j.foodhyd.2024.110029","article-title":"Preparation of soy protein isolate-naringin-chitosan\nprotein gel: Synergistic effect of ohmic heating pre-treatment and\nchitosan addition","volume":"153","author":"Wang","year":"2024","journal-title":"Food Hydrocoll."},{"issue":"1","key":"2026100711070023700_cit4","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1021\/acsami.2c19904","article-title":"Naringin@\nmetal\u2013organic framework as a multifunctional bioplatform","volume":"15","author":"Ge","year":"2023","journal-title":"ACS Appl. Mater. 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Struct."},{"key":"2026100711070023700_cit16","doi-asserted-by":"publisher","first-page":"125160","DOI":"10.1016\/j.carbpol.2026.125160","article-title":"Supramolecular\nself-assembly of an\nherbal fructan and chitosan hydrogel: analysis of the fructan, gel\nstructures and the molecular interaction mechanisms","volume":"381","author":"Zhu","year":"2026","journal-title":"Carbohydr. Polym."},{"key":"2026100711070023700_cit17","doi-asserted-by":"publisher","first-page":"103079","DOI":"10.1016\/j.nantod.2026.103079","article-title":"Bigel microspheres\nencapsulating supramolecular bioactives enabled by electrospraying\nfor colon-targeted delivery and ulcerative colitis therapy","volume":"69","author":"Gu","year":"2026","journal-title":"Nano Today."},{"key":"2026100711070023700_cit18","doi-asserted-by":"publisher","first-page":"158477","DOI":"10.1016\/j.cej.2024.158477","article-title":"Self-assembled\nherbal hydrogel for rectal administration therapy in ulcerative colitis","volume":"503","author":"Lei","year":"2025","journal-title":"Chem. Eng. 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Colloid Interface Sci."},{"issue":"2","key":"2026100711070023700_cit24","doi-asserted-by":"publisher","first-page":"101056","DOI":"10.1016\/j.jpha.2024.101056","article-title":"Supramolecular\nprodrug\ninspired by the Rhizoma Coptidis-Fructus Mume herbal pair alleviated\ninflammatory diseases by inhibiting pyroptosis","volume":"15","author":"Qian","year":"2025","journal-title":"J. Pharm. Anal."},{"key":"2026100711070023700_cit25","doi-asserted-by":"publisher","first-page":"168335","DOI":"10.1016\/j.cej.2025.168335","article-title":"Analogical prediction\nof chiral-regulated self-assembling hydrogel guided by computational\nchemistry and molecular similarity principles to enhance wound healing","volume":"524","author":"Tan","year":"2025","journal-title":"Chem. Eng. 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Crops Prod."},{"key":"2026100711070023700_cit38","doi-asserted-by":"publisher","first-page":"150136","DOI":"10.1016\/j.foodchem.2026.150136","article-title":"Unveiling\nthe molecular interplay: phosvitin as a stabilizer of lactoferrin\nagainst thermal denaturation","volume":"523","author":"Zhang","year":"2026","journal-title":"Food Chem."},{"issue":"4","key":"2026100711070023700_cit39","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/j.pnsc.2022.08.001","article-title":"Preparation, characterization\nand antibacterial property of naringin loaded PLGA nanospheres","volume":"32","author":"Wang","year":"2022","journal-title":"Prog. Nat. Sci.: Mater. 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Chem."},{"issue":"4","key":"2026100711070023700_cit45","doi-asserted-by":"publisher","first-page":"1788","DOI":"10.3390\/molecules28041788","article-title":"Optimisation\nof the extraction process\nof naringin and its effect on reducing blood lipid levels in vitro","volume":"28","author":"Yu","year":"2023","journal-title":"Molecules"},{"issue":"8","key":"2026100711070023700_cit46","doi-asserted-by":"publisher","first-page":"5104","DOI":"10.1021\/acs.molpharmaceut.5c00858","article-title":"Coamorphous System\nof Vitamin B2 and Chlorogenic Acid:\nEnhanced Physicochemical Property and Synergistic Anti-Inflammatory\nPotential","volume":"22","author":"Chen","year":"2025","journal-title":"Mol. 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