{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:53:58Z","timestamp":1791356038821,"version":"4.3.1"},"reference-count":66,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Materials"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Inorganic anticancer drugs such as cisplatin remain central to chemotherapy but are limited by poor tumor selectivity, rapid clearance, and off\u2010target toxicity. We recently developed cationic Pt\n                    <jats:sub>2<\/jats:sub>\n                    L\n                    <jats:sub>4<\/jats:sub>\n                    nanocages with 12\u2010fold higher anticancer activity than cisplatin in PC\u20103M\u2010Pro4 cells\u00a0in vitro, but their positive charge causes rapid extravasation and renal clearance\u00a0in vivo. Here, we re\u2010engineer lipid nanoparticles (LNPs) into charge\u2010reversed lipid nanoparticles (revLNPs) capable of efficiently encapsulating cationic Pt\n                    <jats:sub>2<\/jats:sub>\n                    L\n                    <jats:sub>4<\/jats:sub>\n                    nanocages. Pt\n                    <jats:sub>2<\/jats:sub>\n                    L\n                    <jats:sub>4<\/jats:sub>\n                    \u2010loaded revLNPs retain high cancer\u2010cell uptake and cytotoxicity\u00a0in vitro comparable to the free drug. Following intravenous administration, they show prolonged circulation, reduced vessel\u2010wall leakage, and favorable biodistribution in zebrafish embryos. In mice, revLNPs exhibit a 1.7\u2010fold longer plasma half\u2010life than the clinically approved Onpattro LNP formulation while maintaining characteristic liver and spleen tropism. In zebrafish xenografts, a single injection induces substantial tumor regression, reaching 20% in PC\u20103M\u2010Pro4 and 72% in MDA\u2010MB\u2010231 tumors, and outperforms Lipocisplatin despite a ten\u2010fold lower therapeutic dose. These results establish revLNPs as a broadly applicable delivery platform that overcomes solubility, biodistribution, and pharmacokinetic barriers of cationic inorganic drugs, enabling their effective use in vivo.\n                  <\/jats:p>","DOI":"10.1002\/adma.75288","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:26:44Z","timestamp":1791354404000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Charge\u2010Reversed Lipid Nanoparticles Enable Encapsulation of Pt\n                    <sub>2<\/sub>\n                    L\n                    <sub>4<\/sub>\n                    Nanocages for In vivo Anti\u2010Cancer Treatment"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8463-1680","authenticated-orcid":false,"given":"Renzo A.","family":"Knol","sequence":"first","affiliation":[{"name":"Department of Supramolecular &amp; Biomaterials Chemistry Leiden Institute of Chemistry Leiden University  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bochuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Supramolecular &amp; Biomaterials Chemistry Leiden Institute of Chemistry Leiden University  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduard O.","family":"Bobylev","sequence":"additional","affiliation":[{"name":"Van \u2019t Hoff Institute for Molecular Sciences University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7436-397X","authenticated-orcid":false,"given":"Martina","family":"Farber","sequence":"additional","affiliation":[{"name":"Division of Tumour Biology and Immunology Oncode Institute The Netherlands Cancer Institute  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7970-0066","authenticated-orcid":false,"given":"Petrus C. 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