Austin Evan, Jagdeo Jared
Department of Dermatology, University of California, Davis; Dermatology Service, Sacramento VA Medical Center;
Department of Dermatology, University of California, Davis; Dermatology Service, Sacramento VA Medical Center; Department of Dermatology, State University of New York, Downstate Medical Center.
J Vis Exp. 2018 Aug 17(138):58190. doi: 10.3791/58190.
Photodynamic therapy (PDT) is a medical procedure that involves incubation of an exogenously applied photosensitizer (PS) followed by visible light photoactivation to induce cell apoptosis. The Federal Drug Administration has approved PDT for the treatment of actinic keratosis, and clinical guidelines recommend PDT as a treatment for certain non-melanoma skin cancers and acne vulgaris. PDT is an advantageous therapeutic modality as it is low cost, non-invasive, and associated with minimal adverse events and scaring. In the first step of PDT, a PS is applied and allowed to accumulate intracellularly. Subsequent light irradiation induces reactive oxygen species formation, which may ultimately lead to cell apoptosis, membrane disruption, mitochondrial damage, immune modulation, keratinocyte proliferation, and collagen turnover. Herein, we present an in vitro method to study PDT in an adherent cell line. This treatment protocol is designed to simulate PDT and may be adjusted to studying the use of PDT with various cell lines, photosensitizers, incubation temperatures, or photoactivation wavelengths. Squamous cell carcinoma cells were incubated with 0, 0.5, 1.0, and 2 mM 5-aminolevulinic acid (5-ALA) for 30 min and photoactivated with 417 nm blue light for 1,000 s. The primary outcome measure was apoptosis and necrosis, as measured by annexin-V and 7-aminoactinomycin D flow cytometry. There was a dose-dependent increase in cell apoptosis following thirty-minute incubation of 5-ALA. To achieve high inter-test validity, it is important to maintain consistent incubation and light parameters when performing in vitro PDT experiments. PDT is a useful clinical procedure and in vitro research may allow for the development of novel PSs, optimization of protocols, and new indications for PDT.
光动力疗法(PDT)是一种医疗程序,包括对外源性应用的光敏剂(PS)进行孵育,随后通过可见光光激活诱导细胞凋亡。美国食品药品监督管理局已批准光动力疗法用于治疗光化性角化病,临床指南推荐光动力疗法作为某些非黑素瘤皮肤癌和寻常痤疮的一种治疗方法。光动力疗法是一种具有优势的治疗方式,因为它成本低、非侵入性,且不良事件和瘢痕形成极少。在光动力疗法的第一步,应用一种光敏剂并使其在细胞内积累。随后的光照会诱导活性氧的形成,这最终可能导致细胞凋亡、细胞膜破坏、线粒体损伤、免疫调节、角质形成细胞增殖和胶原蛋白更新。在此,我们展示一种在贴壁细胞系中研究光动力疗法的体外方法。该治疗方案旨在模拟光动力疗法,并且可以进行调整以研究光动力疗法在各种细胞系、光敏剂、孵育温度或光激活波长中的应用。将鳞状细胞癌细胞与0、0.5、1.0和2 mM的5-氨基酮戊酸(5-ALA)孵育30分钟,并用417 nm蓝光光激活1000秒。主要观察指标是通过膜联蛋白-V和7-氨基放线菌素D流式细胞术测量的细胞凋亡和坏死情况。5-ALA孵育30分钟后,细胞凋亡呈剂量依赖性增加。为了实现高测试间效度,在进行体外光动力疗法实验时保持一致的孵育和光照参数很重要。光动力疗法是一种有用的临床程序,体外研究可能有助于开发新型光敏剂、优化方案以及为光动力疗法确定新的适应症。