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We developed LNP@2DG-DON, a liposomal nanoparticle co-delivering glycolysis inhibitor 2DG and GFAT1 inhibitor DON, to enhance antitumor immunity and metabolic targeting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>LNP@2DG-DON nanoparticles were synthesized using the thin-film dispersion method and characterized for size, stability, drug loading, and release profiles. In vitro studies assessed cytotoxicity, apoptosis, migration, and invasion in ASPC-1 and PANC-1 pancreatic cancer cell lines. In vivo efficacy was evaluated in a subcutaneous xenograft mouse model, measuring tumor growth, immune cell infiltration, and survival. Western blotting, flow cytometry, and immunohistochemistry were employed to analyze molecular and cellular mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>LNP@2DG-DON showed uniform size (100\u2013120\u00a0nm), high drug loading (6.84\u20139.27%), and sustained release. It significantly reduced cell viability, induced apoptosis, and inhibited metastasis in vitro. In vivo, it suppressed tumor growth, prolonged survival, and increased CD8+\/NK cell infiltration while reducing immunosuppressive cells. Mechanistically, it downregulated PD-L1\/GFAT1 and activated pro-apoptotic pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The dual-targeting LNP@2DG-DON nanoparticle synergistically combines metabolic and immune modulation, demonstrating superior antitumor effects compared to single-agent therapies. This approach represents a promising strategy for pancreatic cancer treatment, warranting further clinical investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-026-08039-8","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T13:25:24Z","timestamp":1777987524000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy of LNP@2DG-DON liposomal nanoparticles in tumor inhibition and immune activation"],"prefix":"10.1186","volume":"24","author":[{"given":"Jianang","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiale","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Runjie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yueshan","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yueheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7517-1192","authenticated-orcid":false,"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"8039_CR1","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1053\/j.gastro.2023.02.012","volume":"164","author":"EM Stoffel","year":"2023","unstructured":"Stoffel EM, Brand RE, Goggins M. 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