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双功能RGD/R8修饰阿霉素脂质体的制备及其体外评价

, PP. 2103-2107

Keywords: 整合素受体,细胞穿膜肽,脂质体,乳腺癌

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Abstract:

目的制备串联的RGD-R8肽修饰阿霉素(DOX)脂质体(RGD-R8-LP-DOX),对其理化性质进行表征,并研究脂质体与乳腺癌MCF-7细胞的亲和力和增殖抑制作用。方法采用薄膜分散法制备RGD-R8-LP-DOX,研究脂质体的形态、粒径、电位以及包封率;定量细胞摄取实验研究乳腺癌MCF-7细胞对RGD-R8-LP的摄取效率以及对脂质体摄取的影响因素。定性共聚焦实验观察肿瘤细胞对脂质体的摄取。MTT实验研究RGD-R8-LP-DOX对乳腺癌MCF-7细胞的细胞毒性。结果RGD-R8-LP-DOX的粒径为(115.8±11.5)nm,电位为(23.45±4.68)mV,阿霉素的包封率为95.6%。细胞摄取实验结果显示,RGD-R8-LP在4h摄取效率是2h的1.75倍,差异有统计学意义(P<0.05);MCF-7细胞在与脂质体共同孵育4h后对RGD-R8-LP的摄取效率分别是R8-LP、RGD-LP和LP的2.1倍、2.9倍和3.8倍,差异有统计学意义(P<0.01);RGD-R8-LP-DOX与乳腺癌MCF-7细胞孵育24h后的存活率是48h的1.8倍,差异有统计学意义(P<0.05);在给药48h后,R8-LP-DOX、RGD-LP-DOX和LP-DOX的细胞存活率分别是RGD-R8-LP-DOX组的1.6倍、1.8倍和2.4倍,差异有统计学意义(P<0.01)。结论整合素受体特异性配体RGD和细胞穿膜肽R8串联的RGD-R8肽修饰阿霉素脂质体能够有效穿透肿瘤细胞膜进入肿瘤细胞,是一种潜在高效的乳腺癌给药系统。

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