声敏剂Sonoflora介导的声动力治疗小鼠S180肉瘤的实验研究

摘要

目的 探讨声敏剂Sonoflora在S180肉瘤荷瘤小鼠肿瘤组织中的聚集情况及联合超声介导的声动力疗法(SDT)对S180肉瘤的杀伤作用.方法 (1)S180肉瘤荷瘤小鼠腹腔注射10mg/kg的Sonoflora,分别于3、6、12、18、24、48、72h处死小鼠,利用共聚焦显微镜(LSCM)观察Sonoflora在肿瘤及正常肌肉组织中的聚集情况.(2)荷瘤小鼠分别给予超声、Sonoflor及超卢联合Sonoflora处理,以腹腔注射生理盐水作为空白对照组.每2天测量肿瘤体积大小,15天后剥离肿瘤组织,比较瘤体重量.结果 腹腔给药18h后,Sonoflora在肿瘤和正常肌肉组织中的含量均达最高峰,且差异最明显,肿瘤组织中的荧光强度是正常肌肉组织的5.33倍,给药18h为最佳的超声辐射时间.单独使用超声照射(0.4、0.8、1.6W/cm2)或单独注射Sonoflora(10、20、40mg/kg)对小鼠S180肉瘤无明显杀伤作用.Sonoflora(1Omg/ml)联合超声0.4W/cm2(S1U1)、0.8W/cm2(S1 U2)、1.6W/cm2(Sl U3)组的瘤重(g)分别为2.30 ±0.40、0.94 ±0.44、0.88±0.28,分别较空白对照、单纯超声及单纯Sonoflora组显著减少,差异均有统计学意义(P ＜0.05).S1U1组的瘤重均低于S1 U2 、S1 U3组,差异有统计学意义(P＜0.05),而S1 U2组与S1 U3组比较,差异无统计学意义(P＞0.05).结论 Sonoflora具有肿瘤靶向聚集性,其联合超声介导的SDT对小鼠S180肉瘤有明显杀伤作用.%Objective To explore whether sonoflora, a sonosensitizer, can accumulate selectively in the S180 sarcoma of mice and to assess its antitumor effects of sonodynamic therapy ( SDT). Methods S180 sarcoma tumor-bearing mice received intraper-itoneal injection of 10mg/kg of sonoflora and were respectively sacrificed on 3h, 6h, 12h, 18h, 24h, 48h, 72h. Sonoflora gathered in the tumor and normal muscle tissues was observed by confocal microscopy. Tumor-bearing mice were treated with ultrasound, sonoflora and ultrasound combined with sonoflora treatment, respectively. The blank control group was received intraperitoneal injection of saline solution. Tumor size was measured every 2 days and then tumors were stripped for weight comparison on 15th day. Results The sonoflora content of the tumor tissues was 5. 33 times higher than that of the normal muscle tissues at its peak at the 18th hour after intraperitoneal injection, and the difference was the most obvious. It was the best time for SDT. Ultrasound alone(0. 4W/cm2, 0. 8W/cm2, 1. 6W/cm2)or sonoflora alone( 10mg/kg,20mg/kg,40mg/kg)had exhibited no significant effects on tumor size and tumor weight. The weight of tumor tissues in sonoflora ( 10mg/ml) combined with ultrasound with 0. 4W/cm2 ( S1U1 ) ,0. 8W/cm ( S1U2 ) , 1.6W/cm2 (S1U3)were (2. 30 ±0. 40) g, (0. 94 ±0. 44) g and (0. 88 ±0. 28 ) g, respectively. The weight of tumor tissues in S1U1, S1U2 and S1U3 was less than that of control group, ultrasound alone and sonoflora alone group. There were significant statistical differences (P < 0. 05 ). The weight of tumor tissues in S1U1 group had statistical differences from that of S1U2, S1U3 group( P < 0. 05 ). There were no statistical differences between S1U2 and S1U3 group( P > 0. 05). Conclusion Sonoflora has the ability of special accumulation targe-ting to tumor, and ultrasound combined with sonoflora has significant damaging effect on S180 sarcoma.