RGD修饰的载蟾毒灵多级靶向纳米粒对裸鼠人肠癌的抑制作用

Inhibitory action of Bufalin-loaded mPEG-PLGA-PLL-cRGD nanoparticles in colorectal cancer-bearing mice

目的:探讨蟾毒灵多级靶向纳米粒治疗裸鼠肠癌的作用。方法:建立裸鼠皮下移植性肠癌模型并随机分为如下6组:生理盐水(NS)组、蟾毒灵(Bufalin)组、聚乙二醇/聚丙交酯-乙交酯/聚赖氨酸(mPEG-PLGAPLL)纳米粒组(mPEG-PLGA-PLL NPs)、缬氨酸-精氨酸-甘氨酸-天冬氨酸-谷氨酸环肽(cRGD)修饰mPEGPLGAPLL纳米粒组(mPEG-PLGA-PLL-cRGD NPs)、载Bufalin的mPEG-PLGA-PLL纳米粒组(Bufalin-mPEG-PLGAPLL NPs)、载Bufalin的mPEG-PLGA-PLL-cRGD纳米粒组(Bufalin-mPEG-PLGA-PLL-cRGD NPs),经尾静脉给药。比较治疗后各组裸鼠的肿瘤生长情况、肿瘤坏死程度和荷瘤生存时间。结果:治疗后Bufalin组、Bufalin各纳米粒组瘤体均缩小,以经Bufalin-mPEG-PLGA-PLL-cRGD NPs组最为显著;Bufalin各纳米组荷瘤裸鼠平均荷瘤生存时间明显长于其他组(P<0.01);病理结果显示,Bufalin-mPEG-PLGA-PLL-cRGD NPs组肿瘤以重度坏死为主,肿瘤坏死程度显著重于其他各组(P<0.01)。结论:Bufalin多级靶向纳米粒以纳米剂型给药抗癌效果明显增强。

Objective： To determine the targeting efficacy of Bufalin-loaded mPEG-PLGA-PLL-cRGD nanoparticles （Bufalin-mPEG-PLGA-PLL-cRGD NPs） in SW620 colorectal cancer-bearing mice. Methods： The mice were classified into 6 groups on the basis of the solutions they were administered： normal saline （NS） group, Bufalin solution group, mPEG-PLGA- PLL NPs group, mPEG-PLGA-PLL-cRGD NPs group, Bufalin-mPEG-PLGA-PLL NPs group, and Bufalin-mPEG-PLGA-PLL- cRGD NPs group, by injection through the tail vein every other day. After administration, we measured the tumor volume at predetermined intervals and calculated the inhibitory rate. Results： Bufalin-mPEG-PLGA-PLL-cRGD NPs could effectively target the tumor in vivo. The Bufalin-mPEG-PLGA-PLL-cRGD NPs were significantly more effective than other NPs in preventing tumor growth. This study supported the new paradigm for the application of Bufalin to treat colorectal cancer. Conclusion： The anti-cancer effect is greatly enhanced when given in Bufalin-mPEG-PLGA-PLL-cRGD NPs form.