载声敏剂的高分子超声造影剂体内抑瘤效应及其副反应考察

目的通过对比观察载声敏剂血卟啉(HP)的高分子聚合材料聚乳酸羟基乙酸共聚物(PL-GA)超声微泡造影剂(HP-PLGA)的光敏副反应,并观察超声联合该载药微泡对小鼠H22肝癌皮下移植瘤的声动力治疗效果。方法将35只Balb/c小鼠分为5组,分别将不同浓度的HP-PLGA与单纯HP溶液经尾静脉注入各组小鼠体内,阳光辐照后比较观察不同组小鼠眼睛、背部皮肤、尾巴及肝脏产生的副反应。另建立小鼠H22肝癌皮下移植瘤模型,将荷瘤鼠随机分为A、B两大组进行处理,每组30只。A、B组又分为空白对照(C)组、单纯超声辐照(US)组、超声加空白微泡(US+MB)组、超声加单纯HP(US+HP)组和超声加载HPPLGA微泡(US+HP-PLGA)组,隔天处理一次,连续处理3次。A组荷瘤小鼠治疗后15d,比较各组荷瘤小鼠的质量抑瘤率;B组荷瘤小鼠治疗处理后继续喂养,观察各处理组小鼠的生存期。结果注射40mg/ml与20mg/ml单纯HP组小鼠背部皮肤出现明显的红斑焦痂,眼睛红肿,尾巴肿胀,肝脏出现损伤性病理改变,而其他各组无明显反应。与其他各处理组相比较,超声联合载声敏剂PLGA微泡组质量抑瘤率最大,平均生存天数最长,差异具有统计学意义(P<0.05)。结论将声敏剂包裹进高分子造影剂内可以大大降低声敏剂的光敏毒性副反应,且该载声敏剂的高分子造影剂具有明显的体内抑瘤作用,为寻求一种安全、有效、靶向性高、毒副作用小的声动力抗肿瘤方法提供了新的思路和依据。

Detecting on effect of anti-tumor and the side reaction of sonosensitizer-loaded high polymer ultrasound contrast agents

Objective To observe the phototoxicities of hematoporphyrin-loaded PLGA ultrasound contrast agents(HP-PLGA)and to detect the effect of sonodynamic therapy on H22 tumor-bearing mice using HP-PLGA.Methods 35 Balb/c mice were divided into 5 groups,then different concentration of HP-PLGA microbubbles and hematoporphyrin solution were injected into each group of mice;after 15 minutes of sun irradiation,the phototoxicity of the eye,back skin,tail and liver of mice were observed,and the side reaction of liver was detected by HE stain.In addition,60 H22 tumor-bearing mice were divided into two groups(group A and group B).Then the two groups were again divided into five groups for different treatment evenly.The inhibition rate of tumor quality on the 15th day of group A and the life time of group B were detected,respectively.Results In mice injected into hematoporphyrin of 40 mg/ml and 20 mg/ml,the skin of the back reacted by forming a large area of eschar,swelling were observed in eyes and tails,and liver damage were seen in HE staining slice.Conclusions Hematoporphyrin-loaded PLGA ultrasound contrast agents used in sonodynamic therapy could inhibit growth of H22 tumor in mice and significantly reduce the phototoxicity side-effect of hematoporphyrin,which may provided a novel strategy for therapy on tumor.