{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:59:42Z","timestamp":1790791182081,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004230","name":"Korea Polar Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004230","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Breast cancer is the most commonly diagnosed cancer worldwide and a leading cause of cancer\u2010related mortality in women. Despite therapeutic advances, treating advanced or recurrent cases is substantially hampered by drug resistance and the immunosuppressive tumor microenvironment (TME). Here, we report a breakthrough immunotherapeutic strategy using dual\u2010targeted extracellular vesicles from pro\u2010inflammatory M1 macrophages, hyaluronic acid (HA), and cyclic RGD (M1EV_HA\/cRGD), which function as molecular bridges to physically link natural killer (NK) cells with cancer cells. Our platform simultaneously reprograms the hostile TME while activating potent antitumor immunity. HA is incorporated to engage CD44 receptors on NK cells and cRGD peptides to bind tumor\u2010overexpressing integrins, establishing precision dual\u2010targeting. M1EV_HA\/cRGD could physically tether NK cells directly to tumors, and deliver inflammatory cytokines and miRNAs that transform the immunosuppressive TME into a pro\u2010inflammatory battlefield, substantially amplifying immune activation.\n                    <jats:italic>In vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    studies demonstrate that M1EV_HA\/cRGD significantly enhances NK cell clustering at tumor sites, activation status, and cytotoxic killing of breast cancer cells. Unlike single\u2010targeted approaches, this dual\u2010targeting mechanism achieves simultaneous TME reprogramming and enhanced immune\u2010tumor engagement. M1EV_HA\/cRGD is a paradigm shift in solid tumor immunotherapy that directly addresses breast cancer treatment failure, can overcome therapeutic resistance, and substantially improve patient survival outcomes.\n                  <\/jats:p>","DOI":"10.1002\/jev2.70379","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:47:51Z","timestamp":1790790471000},"source":"Crossref","is-referenced-by-count":0,"title":["Dual\u2010Targeted M1 Macrophage Extracellular Vesicles Reprogram the Tumor Microenvironment and Enhance Natural Killer Cell Immunotherapy in Breast Cancer"],"prefix":"10.1002","volume":"15","author":[{"given":"Su Jin","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Bioengineering and Nano\u2010Bioengineering Incheon National University  Incheon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gichan","family":"Baek","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Nano\u2010Bioengineering Incheon National University  Incheon South Korea"},{"name":"Division of Bioengineering Incheon National University  Incheon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suwun","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Nano\u2010Bioengineering Incheon National University  Incheon South Korea"},{"name":"Division of Bioengineering Incheon National University  Incheon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunhee","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Nano\u2010Bioengineering Incheon National University  Incheon South Korea"},{"name":"Division of Bioengineering Incheon National University  Incheon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seongjin","family":"Gwak","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Nano\u2010Bioengineering Incheon National University  Incheon South Korea"},{"name":"Division of Bioengineering Incheon National University  Incheon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Jong","family":"Rhee","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Nano\u2010Bioengineering Incheon National University  Incheon South Korea"},{"name":"Division of Bioengineering Incheon National University  Incheon South Korea"},{"name":"Research Center for Bio Materials &amp; Process Development Incheon National University  Incheon South Korea"},{"name":"Integrated Major in Bio\u2010manufacturing AX Incheon National University  Incheon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"R921","DOI":"10.1016\/j.cub.2020.06.081","article-title":"The Tumor Microenvironment","volume":"30","author":"Anderson N. 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