ArticleChembiochem : a European journal of chemical biology2026
Liposomal Delivery of Cell Impermeable Phototoxic Ru(II) Complexes.
Article in Chembiochem : a European journal of chemical biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Photoactive ruthenium polypyridyl complexes are intensively studied as imaging probes and (photo)therapeutics because of their attractive photophysical properties, including long-lived, oxygen-responsive luminescence, and their ability to sensitize reactive oxygen species (ROS) or to drive photoinduced electron or proton-coupled electron transfer (PCET), which may be advantageous in treating hypoxic tumors where oxygen-dependent 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-active ligand, 1,10-phenanthroline-5,6-dione (phendione), designed as light-switch probes and photocytotoxic agents, including two novel trisheteroleptic complexes (Ru2 and Ru3). 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 (185-194 nm) with a positive surface charge (circa +23 mV), 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-type dependent. In A549 cells, uptake was temperature/energy independent and showed punctate staining in the cytoplasm. Conversely, in HeLa cells, uptake was temperature-dependent, leading to extensive distribution throughout the cytoplasm and notable localization within the nucleus. Following internalization, the Ru2-phendione lipoplex demonstrated significant photo-induced toxicity in HeLa cells upon light irradiation. This work establishes peptide-decorated liposomes as an efficient strategy for delivering cell-impermeable Ru(II) metallodrugs.
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