{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T11:01:41Z","timestamp":1775646101866,"version":"3.50.1"},"reference-count":93,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2026,3,27]]},"abstract":"<jats:p>\n                    Photoactive ruthenium polypyridyl complexes are intensively studied as imaging probes and (photo)therapeutics because of their attractive photophysical properties, including long\u2010lived, oxygen\u2010responsive luminescence, and their ability to sensitize reactive oxygen species (ROS) or to drive photoinduced electron or proton\u2010coupled electron transfer (PCET), which may be advantageous in treating hypoxic tumors where oxygen\u2010dependent therapies often fail. Despite their potential potency, a key limitation is their poor membrane permeation. This study focused on Ru(II) complexes containing the biologically and redox\u2010active ligand, 1,10\u2010phenanthroline\u20105,6\u2010dione (phendione), designed as light\u2010switch probes and photocytotoxic agents, including two novel trisheteroleptic complexes (\n                    <jats:bold>Ru2<\/jats:bold>\n                    and\n                    <jats:bold>Ru3<\/jats:bold>\n                    ). The complexes are water soluble, but completely impermeable to live cells. To address this, we employed peptidoliposomal encapsulation, a strategy not commonly applied to date to photoactive metal complexes. The complexes were successfully incorporated into octaarginine peptide (R8) decorated DOPE\/SM liposomes with a very high encapsulation efficiency (circa 68%) to yield small peptidoliposomes (185\u2013194\u2009nm) with a positive surface charge (circa +23\u2009mV), and photophysical studies indicate that the complex is retained at the liposome aqueous core. The uptake mechanism and resulting cellular localization were found to be unexpectedly cell\u2010type dependent. In A549 cells, uptake was temperature\/energy independent and showed punctate staining in the cytoplasm. Conversely, in HeLa cells, uptake was temperature\u2010dependent, leading to extensive distribution throughout the cytoplasm and notable localization within the nucleus. Following internalization, the Ru2\u2010phendione lipoplex demonstrated significant photo\u2010induced toxicity in HeLa cells upon light irradiation. This work establishes peptide\u2010decorated liposomes as an efficient strategy for delivering cell\u2010impermeable Ru(II) metallodrugs.\n                  <\/jats:p>","DOI":"10.1002\/cbic.202500948","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T05:47:11Z","timestamp":1774590431000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Liposomal Delivery of Cell Impermeable Phototoxic Ru(II) Complexes"],"prefix":"10.1002","volume":"27","author":[{"given":"David","family":"Cullinane","sequence":"first","affiliation":[{"name":"School of Chemical Sciences National Centre for Sensor Research Dublin City University  Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karmel Sofia","family":"Gkika","sequence":"additional","affiliation":[{"name":"School of Chemical Sciences National Centre for Sensor Research Dublin City University  Dublin 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