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We developed a transformative platform based on DNA nanohydrogels enabling dual preservation-isolation through aptamer-guided trehalose delivery in a single workflow, achieving organic solvent-free cryopreservation and high-efficiency isolation via freeze\u2212thaw lethality disparity, termed cryoisolation. The nanohydrogels encapsulate trehalose in hydrated 3D networks, while aptamer-functionalized frameworks enable receptor-specific targeting, driving rapid cellular internalization and release within 2 h, yielding post-thaw viability comparable to that of DMSO while reducing genomic instability (67% fewer differentially expressed genes). The platform can be extended to cryopreserve mesenchymal stem cells (MSCs), confirming its applicability to sensitive primary cells without compromising functional integrity. Molecular-recognition-guided delivery creates differential freeze\u2212thaw survival, enabling label-free isolation of target cells with &amp;gt;95% purity. By redesigning aptamer sequences, this modular platform demonstrates universal applicability, transforming conventional freeze\u2212thaw cycles into precision cell-selection processes.<\/jats:p>","DOI":"10.1021\/acs.biomac.6c00813","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T09:02:05Z","timestamp":1790154125000},"page":"6434-6446","source":"Crossref","is-referenced-by-count":0,"title":["Cell Cryoisolation and Cryopreservation without Any Organic Solvent"],"prefix":"10.1021","volume":"27","author":[{"given":"Leiming","family":"Chu","sequence":"first","affiliation":[{"name":"Hefei University of Technology , , ,","place":["Hefei, China, 230601"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongxiang","family":"Ding","sequence":"additional","affiliation":[{"name":"Anhui University of Science and Technology , , ,","place":["Huainan, China, 232001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Li","sequence":"additional","affiliation":[{"name":"Hefei University of Technology , , ,","place":["Hefei, China, 230601"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Gao","sequence":"additional","affiliation":[{"name":"Hefei University of Technology , , ,","place":["Hefei, China, 230601"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0910-2444","authenticated-orcid":true,"given":"Honglin","family":"Liu","sequence":"additional","affiliation":[{"name":"Hefei University of Technology , , ,","place":["Hefei, China, 230601"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"issue":"6","key":"2026101210522345900_cit1","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1038\/nbt.3889","article-title":"The promise of organ and tissue preservation to transform medicine","volume":"35","author":"Giwa","year":"2017","journal-title":"Nat. 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