Establishing a Robust and Reliable Response from a Potent Osmium‐Based Photosensitizer Via Lipid Nanoformulation. (25th December 2022)

• Record Type: Journal Article
• Authors: Cole, Houston D.; Eroy, Menitte; Roque, John A.; Shi, Ge; Guirguis, Mina; Fakhry, John; Cameron, Colin G.; Obaid, Girgis; McFarland, Sherri A.
• Is Part Of: Photochemistry and photobiology. Volume 99:Number 2(2023)
• Page Start: 751
• Page End: 760
• Publication Date: 2022-12-25
• Subjects: Photochemistry -- Periodicals; Light -- Physiological effect -- Periodicals; 541.35
• DOI: 10.1111/php.13756
• Languages: English
• ISSNs: 0031-8655

Abstract

Abstract: Osmium (Os) based photosensitizers (PSs) are a unique class of nontetrapyrrolic metal‐containing PSs that absorb red light. We recently reported a highly potent Os(II) PS, rac ‐[Os(phen)2 (IP‐4T)](Cl)2, referred to as ML18J03 herein, with light EC50 values as low as 20 pm . ML18J03 also exhibits low dark toxicity and submicromolar light EC50 values in hypoxia in some cell lines. However, owing to its longer oligothiophene chain, ML18J03 is not completely water soluble and forms 1–2 μm sized aggregates in PBS containing 1% DMSO. This aggregation causes variability in PDT efficacy between assays and thus unreliable and irreproducible reports of in vitro activity. To that end, we utilized PEG‐modified DPPC liposomes (138 nm diameter) and DSPE‐mPEG2000 micelles (10.2 nm diameter) as lipid nanoformulation vehicles to mitigate aggregation of ML18J03 and found that the spectroscopic properties important to biological activity were maintained or improved. Importantly, the lipid formulations decreased the interassay variance between the EC50 values by almost 20‐fold, with respect to the unformulated ML18J03 when using broadband visible light excitation ( P = 0.0276). Herein, lipid formulations are presented as reliable platforms for more accurate in vitro photocytotoxicity quantification for PSs prone to aggregation (such as ML18J03) and will be useful for assessing their in vivo PDT effects. Abstract : PEG‐modified DPPC liposomes reduce aggregation and interassay variability in phototoxic response for an osmium‐based photosensitizer.