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

Enabling In Vivo Optical Imaging of an Osmium Photosensitizer by Micellar Formulation.
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DOI:
10.3390/pharmaceutics14112426
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发表时间:
2022-11-10
期刊:
影响因子:
5.4
通讯作者:
Obaid G
Obaid G
中科院分区:
医学2区
文献类型:
--
作者:
Shah D;Eroy M;Fakhry J;Moffat A;Fritz K;Cole HD;Cameron CG;McFarland SA;Obaid G

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锇(Os)基光敏剂(PS)表现出独特的宽,红移吸收,有利于PDT活性在更大的组织深度。我们最近报道了一种具有亚微摩尔缺氧活性的Os(II)PS,rac-[Os(phen)2(IP-4 T)](Cl)2(ML 18 J 03)。ML 18 J 03在PBS中显示出9.8 × 10−5的低发光量子产率,这限制了其体内发光成像的能力。我们最近表明,将ML 18 J 03配制成10.2 nm DSPE-mPEG 2000胶束(Mic-ML 18 J 03)将其发光量子产率提高了两个数量级。在这里,我们证明了Mic-ML 18 J 03在原位AT-84头颈部肿瘤中表现出47倍的累积发光信号改善。我们首次表明,胶束制剂对ML 18 J 03的肿瘤选择性高达11.7倍。此外,Mic-ML 18 J 03未经历PBS中未配制ML 18 J 03观察到的浓度依赖性淬灭,并且制剂降低了PDT期间发射最大值的光谱偏移(方差分别为6.5和27.3)。Mic-ML 18 J 03配方还可将反应性分子物质的产量提高2-3倍。这些研究结果表明,胶束制剂是一种通用的和有效的方法,使体内发光成像选项,否则淬灭,但有前途的PS。
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.
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