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首页> 外文期刊>Journal of photochemistry and photobiology, C. Photochemistry reviews >Enhancing photodynamic therapy of refractory solid cancers: Combining second-generation photosensitizers with multi-targeted liposomal delivery
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Enhancing photodynamic therapy of refractory solid cancers: Combining second-generation photosensitizers with multi-targeted liposomal delivery

机译：增强难治性实体癌的光动力治疗：将第二代光敏剂与多目标脂质体递送相结合

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摘要

Contemporary photodynamic therapy (PDT) for the last-line treatment of refractory cancers such as nasopharyngeal carcinomas, superficial recurrent urothelial carcinomas, and non-resectable extrahepatic cholangiocarcinomas yields poor clinical outcomes and may be associated with adverse events. This is mainly attributable to three factors: (1) the currently employed photosensitizers exhibit suboptimal spectral properties, (2) the route of administration is associated with unfavorable photosensitizer pharmacokinetics, and (3) the upregulation of survival pathways in tumor cells may impede cell death after PDT. Consequently, there is a strong medical need to improve PDT of these recalcitrant cancers. An increase in PDT efficacy and reduction in clinical side-effects may be achieved by encapsulating second-generation photosensitizers into liposomes that selectively target to pharmacologically important tumor locations, namely tumor cells, tumor endothelium, and tumor interstitial spaces. In addition to addressing the drawbacks of clinically approved photosensitizers, this review addresses the most relevant pharmacological aspects that dictate clinical outcome, including photosensitizer biodistribution and intracellular localization in relation to PDT efficacy, the mechanisms of PDT-induced cell death, and PDT-induced antitumor immune responses. Also, a rationale is provided for the use of second-generation photosensitizers such as diamagnetic phthalocyanines (e.g., zinc or aluminum phthalocyanine), which exhibit superior photophysical and photochemical properties, in combination with a multi-targeted liposomal photosensitizer delivery system. The rationale for this PDT platform is corroborated by preliminary experimental data and proof-of-concept studies. Finally, a summary of the different nanoparticulate photosensitizer delivery systems is provided followed by a section on phototriggered release mechanisms in the context of liposomal photosensitizer delivery systems. (C) 2015 Elsevier B.V. All rights reserved.
机译：对于难治性癌症（如鼻咽癌，浅表性复发性尿路上皮癌和不可切除的肝外胆管癌）的最后一线治疗，当代光动力疗法（PDT）的临床疗效较差，并可能与不良事件相关。这主要归因于三个因素：（1）当前使用的光敏剂表现出次优的光谱特性;（2）给药途径与不利的光敏剂药代动力学有关;（3）肿瘤细胞中生存途径的上调可能会阻止细胞死亡在PDT之后。因此，强烈需要改善这些顽固性癌症的PDT。通过将第二代光敏剂封装到脂质体中，可以选择性地靶向药理学上重要的肿瘤部位，即肿瘤细胞，肿瘤内皮和肿瘤间隙，从而实现PDT功效的提高和临床副作用的减少。除了解决临床认可的光敏剂的弊端外，本综述还探讨了指示临床结果的最相关药理学方面，包括与PDT功效有关的光敏剂生物分布和细胞内定位，PDT诱导的细胞死亡的机制以及PDT诱导的抗肿瘤作用。免疫反应。而且，提供了结合多目标脂质体光敏剂递送系统使用具有优异的光物理和光化学性质的第二代光敏剂如抗磁性酞菁（例如锌或铝酞菁）的使用的理由。初步的实验数据和概念验证研究证实了此PDT平台的基本原理。最后，概述了不同的纳米颗粒光敏剂递送系统，随后是脂质体光敏剂递送系统中有关光触发释放机制的部分。 （C）2015 Elsevier B.V.保留所有权利。

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