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ALA和MAL介导的光动力疗法(PDT)治疗皮肤恶性病变的优化及疗效:一项对比研究

Optimization and therapeutic effects of PDT mediated by ALA and MAL in the treatment of cutaneous malignant lesions: A comparative study.

作者信息

Lima Cassio Aparecido, Goulart Viviane Pereira, Bechara Etelvino Jose Henriques, Correa Luciana, Zezell Denise Maria

机构信息

Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Universidade de Sao Paulo, Av. Prof. Lineu Prestes 2242, 05508-000, Sao Paulo-SP, Brazil.

Instituto de Quimica, Universidade de Sao Paulo, Av. Prof. Lineu Prestes 748, 05508-000, Sao Paulo-SP, Brazil.

出版信息

J Biophotonics. 2016 Dec;9(11-12):1355-1361. doi: 10.1002/jbio.201600164. Epub 2016 Sep 22.

Abstract

5-aminolevulinic acid (ALA) and its methylated ester (MAL) are the most common topical agents used in photodynamic therapy (PDT) as precursors of the photosensitizer protoporphyrin IX (PpIX). The induction of newly PpIX depends on incubation time of each photosensitizer in the tissue and the presence of high intralesional porphyrin levels is an important parameter for the PDT effectiveness. This study used laser-induced fluorescence (LIF) spectroscopy to evaluate the optimum time to light exposure of PDT mediated by ALA (20% w/w) and MAL (10% w/w) to treat malignant lesions precursors of cutaneous squamous cell carcinoma induced in mice. The therapeutic effects obtained by optimized ALA- and MAL-PDT were assessed 10 and 20 days after treatments. Higher PpIX levels were evidenced in the lesions photosensitized by ALA than MAL and according to LIF measurements the PDT irradiation was performed, respectively, at 300 and 330 minutes after ALA and MAL incubation. Histopathological analysis evidenced necrosis and epithelial atrophy after 10 days of PDT using both prodrugs, as well as reepitelization and collagen deposition at 20 days. Thus, despite the distinct concentration of ALA and MAL used in the formulation of each photosensitizing cream, PDT mediated by both photosensitizing agents obtained similar therapeutic outcomes.

摘要

5-氨基酮戊酸(ALA)及其甲酯(MAL)是光动力疗法(PDT)中最常用的局部用药,作为光敏剂原卟啉IX(PpIX)的前体。新生成的PpIX的诱导取决于每种光敏剂在组织中的孵育时间,而病灶内高卟啉水平的存在是PDT疗效的一个重要参数。本研究使用激光诱导荧光(LIF)光谱法评估由ALA(20% w/w)和MAL(10% w/w)介导的PDT治疗小鼠皮肤鳞状细胞癌恶性病变前体的最佳光照时间。在治疗后10天和20天评估优化后的ALA-PDT和MAL-PDT所获得的治疗效果。ALA光敏化的病灶中PpIX水平高于MAL,根据LIF测量,在ALA和MAL孵育后分别于300分钟和330分钟进行PDT照射。组织病理学分析表明,使用这两种前体药物进行PDT治疗10天后出现坏死和上皮萎缩,20天后出现上皮再生和胶原沉积。因此,尽管在每种光敏乳膏配方中使用的ALA和MAL浓度不同,但由这两种光敏剂介导的PDT获得了相似的治疗效果。

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