新型载药微泡联合超声靶向爆破技术治疗兔VX2肝癌

New type of drug-loaded microbubbles combined with ultrasound targeted microbubbles destruction for treatment of rabbit VX2 liver cancer

目的观察聚乳酸-羟基乙酸共聚物(PLGA)纳米药物微球-脂质微泡复合体靶向治疗兔VX2肝癌的效果。方法采用双乳化法制备包裹阿霉素的PLGA纳米药物微球(ADM-NP);然后通过碳二亚胺法将ADM-NP连接于氨基脂质微泡(MB-NH2)表面,制备载阿霉素PLGA纳米药物微球-脂质微泡复合体(ADM-NP-MB-NH2)。将30只新西兰大白兔肝VX2移植瘤模型随机分为3组,每组10只。A组为单纯ADM-NP辐照组,经耳缘静脉注入ADM-NP 5ml;B组为混合辐照组,注入5ml ADM-NP与脂质微泡混合溶液;C组为复合体辐照组,注入5ml ADM-NP-MB-NH2。在药物注射完毕的同时,对各组均采用频率1MHz、声强0.5W/cm2的超声波辐照120s。于末次治疗24h后处死荷瘤兔,固定标本并送检;比较各组的肿瘤生长率,计算肿瘤细胞增殖指数(PI)与凋亡指数(AI)。结果A、B、C组肿瘤的生长率分别为(80.13±4.34)%、(59.66±7.93)%及(50.47±9.69)%,C组与A、B组比较差异有统计学意义(P均<0.05);肿瘤PI分别为(74.82±7.25)%、(60.77±8.48)%及(55.94±6.97)%,C组与A、B组比较差异均有统计学意义(P均<0.05);AI分别为(31.70±6.42)%、(50.35±3.82)%及(72.47±5.93)%,C组AI与A、B组比较差异有统计学意义(P均<0.05)。结论采用ADM-NP与脂质微泡复合体联合UTMD治疗兔VX2肝癌可显著提高疗效。

Objective To observe the treatment effect of the complex of PLGA nanosperes with adruanaycin in side （ADM-NP） and lipid microbubhles （MB-NHz） combined with ultrasound targeted microbubbles destruction （UTMD） for rabbit VX2 liver cancer. Methods ADM-NP were prepared with double emulsification method. MB-NH2 were prepared with mechanical shaking. The complex of ADM-NP and MI3-NHs were prepared using carbodiimide method. Totally 30 New Zealand rabbits with VX2 liver cancer were divided into 3 groups （each n= 10）. Rabbits in group A （ADM-NP-I-UT- MD group） were given nanospheres by injecting 5 ml ADM-NP via ear vein, in group B （ADM-NP± MB-NH2 ±UTMD group）were given 5 ml mixing liquor, while in group C （ADM-NP-MB-NH2 -[-UTMD group） were given 5 ml complex liq- uor. All the rabbits were irradiated 120 s with low frequency ultrasound （1 MHz, 0.5 W/cm2） after injection. The rabbits in each group were saerifieed after 24 h, and the samples were examined, then the growth rate （GR）, proliferation index （PI） and apoptotic index （AI） of the VX2 tumor were calculated. Results GR of group A, B and C was （80.13 ± 4.34）%, （59.66±7.93）% and （50.47±9.69）%, PI was （74.82±7.25）%, （60. 77±8.48）% and （55.94±6.97）%, AI was （31.70±6.42）%, （50.35±3.82）% and （72.47±5.93）%, respectively. GR in group C was lower than that in the other two groups （both P〈0.05）, and the PI was the lowest, but AI was the highest in group C （all P〈0.05）. Con- clusion The therapeutic effect for rabbit VX2 cancer can be significantly improved using ADM-NP-MB-NH2 combined with