激光引发喷洒HpD增强肿瘤的光动力效应

Intensifed Effect of Photodynamic Therapy on Tumors through Laser ignited Topical Mini spraying of HpD

光动力学疗法（ＰＤＴ）主要副作用之一是皮肤光敏反应。我们研制了激光引发微型喷药装置，直接喷射给药以减少皮肤光敏反应。以小鼠Ｓ－１８０实体移植瘤为模型。腹腔注射（Ｉ．Ｐ．）和肿瘤表面喷药（Ｓ．Ｔ．）两种给药方法，但剂量相同。用荧光分光光度法检测给药后不同时间内肿瘤、血液和皮肤的ＨｐＤ浓度，发现给药后３ｈ～１６８ｈ肿瘤内ＨｐＤ浓度，Ｓ．Ｔ．法明显高于Ｉ．Ｐ．法（Ｐ＜０．０１），而皮肤ＨｐＤ浓度恰好相反，Ｉ．Ｐ．法高于Ｓ．Ｔ．法。肿瘤与皮肤ＨｐＤ浓度之比，Ｓ．Ｔ．法明显高于Ｉ．Ｐ．法（Ｐ＜０．０１），提示此方法可能提高肿瘤的光动力学效果，减轻皮肤光敏反应和全身损害。两种方法给药３ｈ及２４ｈ后的ＰＤＴ治疗，较对照组均能延迟肿瘤生长（Ｐ＜０．０１），其中以Ｓ．Ｔ．法３ｈ后照光效果最佳，说明该方法确能增强光动力学效应，其机理可能主要是对肿瘤的直接损伤。

Photodynamic therapy (PDT) with hematoporphyrin derivative (HpD) as the photosensitizer is a new treatment for cancers. The major drawback of this procedure is the often resulting skin photosensitivity. Patients must remain in subdued light for four to six weeks to avoid cutaneous phototoxicity. Recently we invented a laser ignited mini spraying device to examine the possibility of reducing the skin photosensitization while maintaining the tumor phototoxic effect by spraying HpD directly into the tumors. A subcutaneously implanted mouse S 180 sarcoma was used as an animal model. HpD was administered either intraperitoneally (I.P.: 5mg/kg. b.w.)or by superficial tumor spray (S.T.: 5mg/kg. b.w). The concentrations of HpD in tumor, skin and blood were analyzed at various intervals after administration by a fluorometric method. The results indicated that at 3 to 168 hours after administration, porphyrin levels in tumors were significantly higher by S.T. than by I.P. (P<0 01), while the concentrations in skin were lower. Ratios of porphyrin concentrations between tumor to skin were much higher for S.T. than for I.P. (P<0 01). Higher porphyrin levels in tumors and lower in normal tissues may indicate a lower skin photosensitivity, systemic cytotoxicity and probably a greater tumor photosensitivity. Tumor volume was measured and the treatment efficacy of PDT was determined by calculation of tumor volume multiplication presented as the number of days required for the tumors to reach 2 and 10 times of their initial volume. Compared with control groups, a significant delay in tumor growth in vivo was observed in mice that received HpD by S.T. and I.P. 3h, 24h before photo irradiation (P<0 01)。 The most significant delay was revealed in the S.T. 3h group among all treated groups. The above mentioned data indicated that superficial tumor spray with HpD may enhance the efficacy of PDT of tumors, worthy of further investigation.