Department of Dermatology, Asahikawa Medical University, 2-1-1-1 Midorigaokahigashi, Asahikawa 078-8510, Japan.
J Dermatol Sci. 2012 Jun;66(3):221-4. doi: 10.1016/j.jdermsci.2012.02.005. Epub 2012 Mar 7.
Although topical photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) is applied for skin tumors including actinic keratosis, Bowen disease, and squamous cell carcinoma, there are no approved photosensitizers in dermatological field in Japan. TONS501 and TONS504 are novel hydrophobic photosensitizers with anionic and cationic chemical characteristics, respectively.
Using 7, 12-dimethylbenz[a]anthracene (DMBA) and 12-ο-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin papilloma model, we compared the efficacy of ALA-, TONS501-, and TONS504-PDT on the skin tumor regression.
Following application of ALA, TONS501, TONS504 ointment or TONS501 lotion on DMBA- and TPA-induced mouse papillomas, 670 nm laser irradiation by LD670-05 diode laser was performed. Then tumor regression rate was calculated at the indicated time.
The anti-tumor effect of ALA, TONS501, and TONS504 ointment was detected at 24 h and the maximal response was observed at 3 day following the PDT treatment. The maximal response was observed at 150 J/cm(2) irradiation in all 3 photosensitizers. Although both ALA, TONS501 (ointment)-PDT showed more potent anti-tumor effect compared with that of TONS504 ointment or TONS501 lotion, no significant difference was detected between ALA ointment and TONS501 ointment.
A novel TONS501ointment-PDT shows potent anti-tumor effect on DMBA- and TPA-induced mouse skin papilloma and might be more useful for the clinical applications.
尽管使用 5-氨基酮戊酸(ALA)的局部光动力疗法(PDT)可用于治疗包括光化性角化病、鲍恩病和鳞状细胞癌在内的皮肤肿瘤,但在日本,皮肤科领域尚无批准的光敏剂。TONS501 和 TONS504 是具有阴离子和阳离子化学特性的新型疏水性光敏剂。
我们使用 7,12-二甲基苯并[a]蒽(DMBA)和 12-氧十四烷酰佛波醇-13-乙酸酯(TPA)诱导的小鼠皮肤乳头瘤模型,比较了 ALA、TONS501 和 TONS504-PDT 对皮肤肿瘤消退的疗效。
在 DMBA 和 TPA 诱导的小鼠乳头瘤上应用 ALA、TONS501、TONS504 软膏或 TONS501 洗剂后,用 LD670-05 二极管激光进行 670nm 激光照射。然后在指定时间计算肿瘤消退率。
ALA、TONS501 和 TONS504 软膏的抗肿瘤作用在 PDT 治疗后 24 小时即可检测到,最大反应在 3 天观察到。在所有 3 种光敏剂中,照射 150J/cm²时均可达到最大反应。虽然与 TONS504 软膏或 TONS501 洗剂相比,ALA、TONS501(软膏)-PDT 显示出更强的抗肿瘤作用,但 ALA 软膏和 TONS501 软膏之间未检测到显著差异。
新型 TONS501 软膏-PDT 对 DMBA 和 TPA 诱导的小鼠皮肤乳头瘤具有强大的抗肿瘤作用,可能更适用于临床应用。