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目的开发新一代用于光动力学疗法的光敏剂──锌酞菁，并对其抗肿瘤机理进行初步探讨。方法以红光为光源进行体内、外光动力学效应研究，以第一代血卟啉类光敏剂（ＨＰＳ）为阳性对照；以耳指数反映锌酞菁皮肤光敏毒性；光镜及电镜下观察Ｕ１４肿瘤细胞在光动力学治疗下形态学改变。结果锌酞菁在光照强度为５．４Ｊ／ｃｍ２，照光波长６００～７５０ｎｍ时，能显著杀伤ＦＧＣ８５、ＳＭＭＣ７７２１和ＳＧＣ７９０１，ＩＣ５０分别为０．８３６，１．２３７和１．４０８μｇ／ｍｌ；在体光动力学治疗结果显示，锌酞菁（２ｍｇ／ｋｇ，光照剂量２５２Ｊ／ｃｍ２，腹腔给药后２ｄ照光），对Ｕ１４和Ｓ１８０实体瘤抑瘤率分别为７６．７％和６８．７％，而阳性对照组（１６ｍｇ／ｋｇ，余同上）则分别为３６．３％和５３．２％（Ｐ＜０．００１）。锌酞菁暗反应毒性低，无光照时没有细胞毒性，对小鼠皮肤光敏毒性比ＨＰＳ低，给药后３天即可消失。光镜及电镜下观察到Ｕ１４肿瘤在锌酞菁光敏治疗后，细胞核显著改变，染色质凝集边聚，核固缩及相继出现核破裂、凋亡小体形成等符合程序性细胞死亡的形态学特点，且以上改变在光敏治疗后１０ｍｉｎ即可观察到，故锌酞菁可通过诱导肿瘤细胞凋亡引起肿瘤细胞的快?
Objective To develop a new generation of photosensitizer for photodynamic therapy, zinc phthalocyanine, and to study its anti-tumor mechanism. Methods The photodynamic effect in vivo and in vitro were studied using red light as the light source. The first generation hematoporphyrin photosensitizer (HPS) was used as the positive control. The ear index was used to determine the skin phototoxicity of zinc phthalocyanine. The light and electron microscopic observations U14 tumor cells under photodynamic therapy morphological changes. Results The results showed that zinc phthalocyanine could significantly kill FGC85, SMMC7721 and SGC7901 at the light intensity of 5.4 J / cm2 and illumination wavelength of 600-750 nm with IC50 of 0.836, 1.237 and 1.408 μg / ml, respectively. In bulk light Kinetic treatment results showed that the inhibitory rates of zinc phthalocyanine (2mg / kg, light dose 252J / cm2, 2d after intraperitoneal administration) on the solid tumors of U14 and S180 were 76.7% and 68.7%, respectively. Positive control group (16mg / kg, the same above) were 36.3% and 53.2% (P <0.001). Zinc phthalocyanine dark reaction toxicity is low, no light without cytotoxicity, photosensitivity to mouse skin than HPS low, 3 days after administration can disappear. Under light microscope and electron microscope, U14 tumors showed significant changes in nuclei after photochemical treatment with zinc phthalocyanine, chromatin condensation and edge clustering, nuclear pyknosis and subsequent nuclear rupture and apoptotic body formation in accordance with the morphological changes of programmed cell death Characteristics, and the above changes can be observed 10min after the photosensitive treatment, so zinc phthalocyanine can induce tumor cell apoptosis by inducing fast?