Enabling In Vivo Optical Imaging of an Osmium Photosensitizer by Micellar Formulation

Abstract

Osmium (Os)-based photosensitizers (PSs) exhibit unique broad, red-shifted absorption, favoring PDT activity at greater tissue depths. We recently reported on a potent Os(II) PS, rac-[Os(phen)2(IP-4T)](Cl)2 (ML18J03) with submicromolar hypoxia activity. ML18J03 exhibits a low luminescence quantum yield of 9.8 × 10−5 in PBS, which limits its capacity for in vivo luminescence imaging. We recently showed that formulating ML18J03 into 10.2 nm DSPE-mPEG2000 micelles (Mic-ML18J03) increases its luminescence quantum yield by two orders of magnitude. Here, we demonstrate that Mic-ML18J03 exhibits 47-fold improved accumulative luminescence signals in orthotopic AT-84 head and neck tumors. We show, for the first time, that micellar formulation provides up to 11.7-fold tumor selectivity for ML18J03. Furthermore, Mic-ML18J03 does not experience the concentration-dependent quenching observed with unformulated ML18J03 in PBS, and formulation reduces spectral shifting of the emission maxima during PDT (variance = 6.5 and 27.3, respectively). The Mic-ML18J03 formulation also increases the production of reactive molecular species 2–3-fold. These findings demonstrate that micellar formulation is a versatile and effective approach to enable in vivo luminescence imaging options for an otherwise quenched, yet promising, PS.

Increasing the Dye Payload of Cetuximab-IRDye800CW Enables Photodynamic Therapy

“…As previously described, anthracene-9,10-dipropionic acid (ADPA) was used as a colorimetric probe at 378 nm to detect singlet oxygen generation. 10 , 20 , 21 While the fluorescence changes in ADPA for singlet oxygen detection are more sensitive than the absorbance changes, absorbance was monitored as to avoid fluorescence artifacts arising from other factors such as contaminants or quenching. 37 It was found that ADPA decreased in absorbance at 378 nm for all samples ( Figure 4 A).…”

“…For SOSG and HPF samples, fluorescence was measured with 460 nm excitation and 530 nm emission (bottom read, 100 gain, 20 μs integration time). ADPA was used as a colorimetric probe for singlet oxygen generation as previously described. ,, The absorbance of ADPA samples was measured at 378 nm (25 flashes, 0 ms settle time).…”

“…ADPA was used as a colorimetric probe for singlet oxygen generation as previously described. 10 , 20 , 21 The absorbance of ADPA samples was measured at 378 nm (25 flashes, 0 ms settle time).…”

Nanoformulation of Lipophilic Osmium Photosensitizers in Liposomes and Micelles as a General Strategy for Improving Reproducibility and Reducing Quenching†

“…PI values for lipid formulations of ML18J03 are (with broadband visible light) as high as 1.3 × 10 4 and 4.4 × 10 4 for liposomal and micellar formulations, respectively. Micellar formulation of ML18J03 has also been used recently to enable in vivo imaging of head and neck tumors due to enhanced tumor selectivity and luminescence (4).…”

Drug Delivery in Photodynamic Therapy

“…This formulation not only improved the luminescence of the photosensitizer but also increased its tumor selectivity. By encapsulating the photosensitizer within micelles, researchers were able to enhance its accumulation in tumor tissues and achieve a higher level of selectivity, addressing the challenge posed by the photosensitizer’s low-luminescence quantum yield [ 1 ].…”