Nanolipid Formulations of Benzoporphyrin Derivative: Exploring the Dependence of Nanoconstruct Photophysics and Photochemistry on Their Therapeutic Index in Ovarian Cancer Cells.
Nanolipid Formulations of Benzoporphyrin Derivative: Exploring the Dependence of Nanoconstruct Photophysics and Photochemistry on Their Therapeutic Index in Ovarian Cancer Cells.
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DOI：
10.1111/php.13002
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发表时间：
2019-01
影响因子：
3.3
通讯作者：
Hasan T
中科院分区：
文献类型：
--
作者：
Obaid G;Jin W;Bano S;Kessel D;Hasan T
随着基于光激活、光动力治疗 (PDT) 的纳米结构、光纳米药物 (PNM) 的设计和应用的迅速兴起，确定光敏剂的光化学和光物理表征的传统方法是否与评估新的 PNM 相关以智能地指导其设计的需求尚未得到满足。作为模型系统，我们以苯并卟啉衍生物 (BPD) Visudyne® 的临床制剂为基础，开发了一组纳米脂质制剂，其中包含具有不同化学、光化学和光物理性质的新脂化 BPD 化学变体。这些是 16:0 和 20:0 溶血磷酸胆碱-BPD (16:0/20:0 BPD-PC)、DSPE-PEG-BPD 和 BPD-胆固醇。我们发现 Visudyne® 是对 OVCAR-5 细胞光毒性最强的制剂，效果最差的是脂质体 DSPE-PEG-BPD。然而，这些差异与它们的光学、光物理和光化学特性并不匹配，因为 Visudyne 的静态 BPD 猝灭最高，而且单线态氧的产生量也最低。此外，我们确定 OVCAR-5 细胞光毒性也与任何纳米脂质制剂中的光敏剂光漂白率和荧光量子产率无关。这些发现为未来对光动力纳米结构的亚细胞靶点和光毒性分子机制进行关键研究提供了依据，作为预测功效的更可靠的预后替代品，以便适当和智能地指导其设计。光纳米药物（用于光动力疗法（PDT）的光激活纳米结构）的光物理和光化学评估被认为可以预测其作为光动力剂的效力。作为模型系统，我们在这里制备了一组苯并卟啉衍生物及其各自的脂质化变体的纳米脂质制剂，以评估卵巢癌细胞的光物理和光化学特性以及治疗指数之间的相关性。我们的结论是，光物理学和光化学本身不足以评估新兴光纳米药物的效力和预测功效，并且对亚细胞靶标的机制洞察必须纳入评估过程，以加快开发并最大程度地减少失败。
With the rapidly emerging designs and applications of light-activated, photodynamic therapy (PDT)-based nanoconstructs, photonanomedicines (PNMs), an unmet need exists to establish whether conventional methods of photochemical and photophysical characterization of photosensitizers are relevant for evaluating new PNMs in order to intelligently guide their design. As a model system, we build on the clinical formulation of benzoporphyrin derivative (BPD), Visudyne®, by developing a panel of nanolipid formulations entrapping new lipidated chemical variants of BPD with differing chemical, photochemical and photophysical properties. These are 16:0 and 20:0 lysophosphocholine-BPD (16:0/20:0 BPD-PC), DSPE-PEG-BPD and BPD-cholesterol. We show that Visudyne® was the most phototoxic formulation to OVCAR-5 cells, and the least effective was liposomal DSPE-PEG-BPD. However, these differences did not match their optical, photophysical and photochemical properties, as the static BPD quenching was highest in Visudyne, which also exhibited the lowest generation of singlet oxygen production. Furthermore, we establish that OVCAR-5 cell phototoxicity also does not correlate with rates of photosensitizer photobleaching and fluorescence quantum yields in any nanolipid formulations. These findings warrant critical future studies into subcellular targets and molecular mechanisms of phototoxicity of photodynamic nanoconstructs, as more reliable prognostic surrogates for predicting efficacy in order to appropriately and intelligently guide their design. Photophysical and photochemical evaluation of photonanomedicines – light activated nanoconstructs used for photodynamic therapy (PDT) – is considered to be predictive of their potency as photodynamic agents. As a model system, we here prepare a panel of nanolipid formulations of benzoporphyrin derivative and its respective lipidated variants to assess the correlations between the photophysical and photochemical properties, and therapeutic indices in ovarian cancer cells. We concludes that photophysics and photochemistry alone are insufficient to evaluate potency and predict efficacy of emerging photonanomedicines, and that mechanistic insights into subcellular targets must be included in the evaluation process to expedite development and minimize failures.
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影响因子：
3.3
作者：
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通讯作者：
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影响因子：
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影响因子：
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作者：
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