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However, its clinical intervention for solid tumors is hindered by the limited expression of tumor\u2010specific antigens. Herein, lipid\u2010PEG conjugated hyaluronic acid (HA) materials (HA\u2010PEG\u2010Lipid) for the simple ex\u2010vivo surface coating of NK cells is developed for 1) lipid\u2010mediated cellular membrane anchoring via hydrophobic interaction and thereby 2) sufficient presentation of the CD44 ligand (i.e., HA) onto NK cells for cancer targeting, without the need for genetic manipulation. Membrane\u2010engineered NK cells can selectively recognize CD44\u2010overexpressing cancer cells through HA\u2010CD44 affinity and subsequently induce in situ activation of NK cells for cancer elimination. Therefore, the surface\u2010engineered NK cells using HA\u2010PEG\u2010Lipid (HANK cells) establish an immune synapse with CD44\u2010overexpressing MIA PaCa\u20102 pancreatic cancer cells, triggering the \u201crecognition\u2010activation\u201d mechanism, and ultimately eliminating cancer cells. Moreover, in mouse xenograft tumor models, administrated HANK cells demonstrate significant infiltration into solid tumors, resulting in tumor apoptosis\/necrosis and effective suppression of tumor progression and metastasis, as compared to NK cells and gemcitabine. Taken together, the HA\u2010PEG\u2010Lipid biomaterials expedite the treatment of solid tumors by facilitating a sequential recognition\u2010activation mechanism of surface\u2010engineered HANK cells, suggesting a promising approach for NK cell\u2010mediated immunotherapy.<\/jats:p>","DOI":"10.1002\/smll.202306738","type":"journal-article","created":{"date-parts":[[2023,12,31]],"date-time":"2023-12-31T23:50:33Z","timestamp":1704066633000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Surface Engineering of Natural Killer Cells with CD44\u2010targeting Ligands for Augmented Cancer Immunotherapy"],"prefix":"10.1002","volume":"20","author":[{"given":"Sungjun","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Chemical &amp; Biochemical Engineering Dongguk University 30, Pildong\u2010ro 1\u2010gil, Jung\u2010gu Seoul 04620 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujin","family":"Li","sequence":"additional","affiliation":[{"name":"Division in Anatomy and Developmental Biology Department of Oral Biology Taste Research Center Oral Science Research Center BK21 FOUR Project Yonsei University College of Dentistry 50\u20131 Yonsei\u2010ro, Seodaemun\u2010gu Seoul 03722 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok Kumar","family":"Jangid","sequence":"additional","affiliation":[{"name":"Department of Chemical &amp; Biochemical Engineering Dongguk University 30, Pildong\u2010ro 1\u2010gil, Jung\u2010gu Seoul 04620 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Won","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Chemical &amp; Biochemical Engineering Dongguk University 30, Pildong\u2010ro 1\u2010gil, Jung\u2010gu Seoul 04620 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong\u2010Joon","family":"Lee","sequence":"additional","affiliation":[{"name":"Division in Anatomy and Developmental Biology Department of Oral Biology Taste Research Center Oral Science Research Center BK21 FOUR Project Yonsei University College of Dentistry 50\u20131 Yonsei\u2010ro, Seodaemun\u2010gu Seoul 03722 Republic of Korea"},{"name":"Department of Oral Histology Dankook University College of Dentistry 119, Dandae\u2010ro, Dongnam\u2010gu Cheonan 31116 Chungcheongnam\u2010do Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han\u2010Sung","family":"Jung","sequence":"additional","affiliation":[{"name":"Division in Anatomy and Developmental Biology Department of Oral Biology Taste Research Center Oral Science Research Center BK21 FOUR Project Yonsei University College of Dentistry 50\u20131 Yonsei\u2010ro, Seodaemun\u2010gu Seoul 03722 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3678-2078","authenticated-orcid":false,"given":"Kyobum","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Chemical &amp; 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