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Among various triggers, cellulase has recently attracted increasing attention because of its unique biological distribution; it is absent in humans but produced by specific micro-organisms and insects. Herein, we report a cellulase-responsive drug delivery carrier based on terminally alkylated cello-oligosaccharide assemblies. Among the assemblies examined, terminally hexylated cello-oligosaccharides with the cellulose I allomorph (CELI-C6) exhibited the highest loading capacity for the hydrophobic antibiotic rifampicin, likely driven by the hydrophobic effect. Upon exposure to cellulase, CELI-C6 underwent rapid degradation, leading to efficient release of rifampicin. This rapid response likely originates from the low degree of polymerization of the constituent cello-oligosaccharide chains, for which only one or a few hydrolytic cleavage events induce solubilization. Notably, rifampicin release was selectively triggered by cellulase containing cellobiohydrolase activity, whereas negligible release was observed with other enzymes. The released rifampicin exhibited potent antibacterial activity against Escherichia coli, whereas loading rifampicin into CELI-C6 effectively suppressed its antibacterial activity in the absence of cellulase. These results demonstrate that CELI-C6 functions as a carrier enabling enzyme-selective, sharp, and rapid release of hydrophobic drugs, offering opportunities for biomedical and agricultural applications.<\/jats:p>","DOI":"10.1021\/acsabm.6c01424","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T04:27:57Z","timestamp":1788409677000},"page":"8899-8906","source":"Crossref","is-referenced-by-count":0,"title":["Cello-oligosaccharide Nanoarchitectonics: Drug Carriers with High Responsiveness to Cellulase"],"prefix":"10.1021","volume":"9","author":[{"given":"Jun Seok","family":"Lee","sequence":"first","affiliation":[{"name":"Institute of Science Tokyo , , 2-12-1-H-121 Ookayama, Meguro-ku , ,","place":["Tokyo, Japan, 152-8550"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1493-1896","authenticated-orcid":true,"given":"Yuuki","family":"Hata","sequence":"additional","affiliation":[{"name":"Institute of Science Tokyo , , 2-12-1-H-121 Ookayama, Meguro-ku , ,","place":["Tokyo, Japan, 152-8550"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2093-0455","authenticated-orcid":true,"given":"Thomas","family":"Sakata","sequence":"additional","affiliation":[{"name":"Institute of Science Tokyo , , 2-12-1-H-121 Ookayama, Meguro-ku , ,","place":["Tokyo, Japan, 152-8550"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4867-8625","authenticated-orcid":true,"given":"Takeshi","family":"Serizawa","sequence":"additional","affiliation":[{"name":"Institute of Science Tokyo , , 2-12-1-H-121 Ookayama, Meguro-ku , ,","place":["Tokyo, Japan, 152-8550"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"issue":"4976","key":"2026092100090699700_cit1","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1126\/science.2218494","article-title":"New Methods of Drug Delivery","volume":"249","author":"Langer","year":"1990","journal-title":"Science"},{"issue":"1","key":"2026092100090699700_cit2","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s12951-021-01214-7","article-title":"Nanomaterials and Nanotechnology for the Delivery of Agrochemicals: Strategies towards Sustainable Agriculture","volume":"20","author":"An","year":"2022","journal-title":"J. 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