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Inspired by this principle, we developed multicompartmentalized artificial cells using liquid\u2013liquid phase separation (LLPS) to regulate cascade enzymatic reactions. Glucose oxidase (GOx) and horseradish peroxidase (HRP) were separately encapsulated into PEGylated and non\u2010PEGylated liposomes, forming enzyme\u2010loaded nanoreactors. These nanoreactors were assembled within a PEG\/dextran aqueous two\u2010phase system, allowing controlled spatial arrangement of nanoreactors. Depending on PEGylation, liposomes localized either at the microdroplet interface or inside the lumen, creating four distinct artificial cell models in one step. Among them, the organization with GOx\u2010loaded liposomes at the interface (Models 1 and\u00a02) exhibited the highest catalytic efficiency. This enhancement arose from improved substrate accessibility, reduced diffusion barriers, and optimized nanoreactor separation. Other models with less favorable spatial arrangements showed slower reaction rates. Our results highlight how spatial organization within artificial cells can critically influence cascade reaction performance. This modular and biomimetic strategy offers a versatile platform for designing synthetic cells, programmable biocatalysts, and functional microreactors for applications in biosensing, metabolic engineering, and therapeutics.<\/jats:p>","DOI":"10.1002\/smll.202511184","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T11:19:27Z","timestamp":1767871167000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Spatiotemporal Organization of Nanoreactors in Artificial Cells by Liquid\u2013Liquid Phase Separation for Regulation of Cascade Enzymatic Reactions"],"prefix":"10.1002","volume":"22","author":[{"given":"Xiaohan","family":"Zhou","sequence":"first","affiliation":[{"name":"The Tenth Affiliated Hospital Southern Medical University (Dongguan People's Hospital) Dongguan 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