Anand Sanjay, Yasinchak Anton, Govande Mukul, Shakya Sajina, Maytin Edward V
Department of Biomedical Engineering, Lerner Research Institute.
Dermatology and Plastic Surgery Institute.
Proc SPIE Int Soc Opt Eng. 2019 Feb;10860. doi: 10.1117/12.2511646. Epub 2019 Feb 28.
Aminolevulinic acid based photodynamic therapy (ALA-PDT) is a popular and efficacious treatment for actinic keratosis (AK). However, standard PDT can elicit stinging pain during illumination, and hence is not always favored by patients. In a new regimen called metronomic PDT (mPDT), similar to daylight PDT but using blue light, the illumination is delivered concurrently with ALA application rather than after a 1-hour pre-incubation (conventional regimen, cPDT). In the clinic, mPDT is not only painless but also nearly as effective as cPDT for AK lesion clearance. In this investigation, a murine AK model (generated by repeated UVB exposure) was treated with either mPDT or cPDT. Lesion clearance was followed by area measurement, and samples were harvested for mechanistic analyses. Compared to pretreatment (100%), the average lesion area was reduced to 47% and 32% in cPDT, and to 57% and 40% in mPDT at 1- and 2-weeks post PDT, respectively. Relative to untreated controls, enhanced cell death (histomorphology by H&E staining and apoptosis by TUNEL assay), and generation of Reactive Oxygen Species (ROS; CM-H2DCFDA staining) were observed in both cPDT and mPDT samples. Activation of cleaved Caspase-3 was specifically observed only in cPDT samples. Immunomodulation by inflammatory cells was observed by enhanced infiltration/retention of neutrophils and macrophages in metronomic PDT samples. Our results suggest that metronomic PDT can be just as effective as conventional PDT for treatment of AK, but the mechanisms may be quite different.
基于氨基乙酰丙酸的光动力疗法（ALA-PDT）是治疗光化性角化病（AK）的一种常用且有效的方法。然而，标准的光动力疗法在光照过程中会引起刺痛，因此并非总是受到患者青睐。在一种名为节律性光动力疗法（mPDT）的新方案中，类似于日光光动力疗法但使用蓝光，光照与ALA应用同时进行，而不是在1小时预孵育后（传统方案，cPDT）。在临床上，mPDT不仅无痛，而且在清除AK病变方面几乎与cPDT一样有效。在本研究中，用mPDT或cPDT治疗了小鼠AK模型（通过重复紫外线B照射产生）。通过面积测量跟踪病变清除情况，并采集样本进行机制分析。与预处理时（100%）相比，在光动力疗法后1周和2周时，cPDT组的平均病变面积分别降至47%和32%，mPDT组分别降至57%和40%。相对于未治疗的对照组，在cPDT和mPDT样本中均观察到细胞死亡增加（苏木精和伊红染色的组织形态学以及TUNEL检测的细胞凋亡）和活性氧（ROS；CM-H2DCFDA染色）的产生。仅在cPDT样本中特异性观察到裂解的半胱天冬酶-3的激活。通过节律性光动力疗法样本中中性粒细胞和巨噬细胞浸润/滞留增加观察到炎症细胞的免疫调节作用。我们的结果表明，节律性光动力疗法在治疗AK方面可能与传统光动力疗法一样有效，但机制可能大不相同。
