载吲哚菁绿聚合物纳米粒的光动力治疗及其抗表皮生长因子偶联物对 CD1 小鼠皮肤癌的疗效。
Photodynamic therapeutic effect of indocyanine green entrapped in polymeric nanoparticles and their anti-EGFR-conjugate in skin cancer in CD1 mice.
机构信息
Cancer Biology Laboratory, Center of Excellence for Advanced Sciences, National Research Center, Cairo, Egypt; Department of Biochemistry, National Research Center, Cairo, Egypt.
出版信息
Photodiagnosis Photodyn Ther. 2013 Dec;10(4):446-59. doi: 10.1016/j.pdpdt.2013.03.013. Epub 2013 Apr 30.
BACKGROUND
Indocyanine green (ICG) is a promising photosensitive agent for photodynamic therapy (PDT) of tumors. Encapsulating ICG dye in polymeric nanoparticles based on PEBBLE technology forming (ICG-PEBBLE) could improve the aqueous stability of the entrapped ICG molecules. The study objective is to investigate the PDT effect of free ICG-PEBBLE and its Anti-EGFR conjugate.
METHODS
Skin squamous cell carcinoma was induced in CD1 mice by dimethylbenzanthracene (DMBA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) followed by a PDT protocol for four weeks.
RESULTS
PDT using ICG-PEBBLE or ICG-PEBBLE-Anti-EGFR decreased skin tumor sizes. Our findings revealed that the inflammatory mediators tumor necrosis factor (TNF-α), nitric oxide (NO), cycloxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), the angiogenic mediator vascular endothelial growth factor (VEGF), and proliferating cell nuclear antigen (PCNA) were decreased, while apoptosis, caspase-3 and histone acetylation were induced in tumor bearing groups after PDT using both of ICG-PEBBLE or ICG-PEBBLE-Anti-EGFR.
CONCLUSION
The present study indicated the effectiveness of PDT using ICG-PEBBLE or ICG-PEBBLE-Anti-EGFR as an inhibitor modality for tumor size, apoptosis, angiogenesis and tumor inflammation. The conjugating of ICG-PEBBLE to anti-EGFR was found to be more effective in inhibiting VEGF and in increasing caspase-3 compared to free ICG-PEBBLE, but there were no other preferential PDT efficacy.
背景
吲哚菁绿（ICG）是一种很有前途的光敏剂，可用于肿瘤的光动力疗法（PDT）。基于 PEBBLE 技术将 ICG 染料封装在聚合物纳米粒子中形成（ICG-PEBBLE）可以提高包封的 ICG 分子的水稳定性。本研究的目的是研究游离 ICG-PEBBLE 及其抗 EGFR 缀合物的 PDT 效应。
方法
通过二甲基苯蒽（DMBA）和 12-O-十四烷酰佛波醇-13-乙酸酯（TPA）在 CD1 小鼠中诱导皮肤鳞状细胞癌，然后进行四周的 PDT 方案。
结果
使用 ICG-PEBBLE 或 ICG-PEBBLE-抗 EGFR 的 PDT 可减小皮肤肿瘤的大小。我们的研究结果表明，炎性介质肿瘤坏死因子（TNF-α）、一氧化氮（NO）、环氧化酶-2（COX-2）和 5-脂氧合酶（5-LOX）、血管生成介质血管内皮生长因子（VEGF）和增殖细胞核抗原（PCNA）减少，而在 PDT 后，肿瘤携带组中的细胞凋亡、半胱天冬酶-3 和组蛋白乙酰化被诱导。
结论
本研究表明，使用 ICG-PEBBLE 或 ICG-PEBBLE-抗 EGFR 的 PDT 作为肿瘤大小、凋亡、血管生成和肿瘤炎症的抑制方式是有效的。与游离 ICG-PEBBLE 相比，将 ICG-PEBBLE 与抗 EGFR 缀合发现更能有效抑制 VEGF 并增加 caspase-3，但没有其他优先的 PDT 疗效。
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