论文部分内容阅读
本文制备光敏感型活性氧自由基(reactive oxygen species,ROS)响应脂质体,研究其体外抗肿瘤活性。采用硫酸铵梯度法制备共输送光敏剂八丁氧基酞菁钯[1,4,8,11,15,18,22,25-octabutoxypalladium phthalocyanine,Pd PC(OBu)_8]与盐酸多柔比星(doxorubicin hydrochloride,DOX)的脂质体[liposome loaded with Pd PC(OBu)_8and DOX,LPD],考察LPD的粒径、zeta电位、透射电镜照片、光敏感型ROS响应药物的光响应释放及在血清中稳定性,进一步考察LPD在MCF-7细胞中的细胞毒性、细胞摄取及细胞内单线态氧(singlet oxygen,~1O_2)水平。结果显示,LPD的粒径为(169.3±1.2)nm,PDI为0.198±0.003,粒径均匀,zeta电位为(-39.8±0.8)m V。LPD具有良好的光响应释放特性,在730 nm激光以300 m W·cm~(-2)光照强度下,5 min内DOX释放率达到95.5%。LPD能显著促进DOX的细胞摄取,而且光照时细胞内能产生大量~1O_2。与游离DOX相比,LPD未光照时IC_(50)下降67.9%,光照时IC_(50)下降85.7%。因此,光敏ROS响应脂质体是具有前景的给药系统。
In this paper, a photoactive reactive oxygen species (ROS) response liposome was prepared and its anti-tumor activity in vitro was studied. Aqueous solution of 1,4-butanedioic acid phthalocyanine palladium [1,4,8,11,15,18,22,25-octabutoxypalladium phthalocyanine (Pd PC (OBu) _8]) and doxorubicin hydrochloride (DOX, LPD) of doxorubicin hydrochloride (DOX), the particle size, zeta potential, transmission electron micrographs of LPD, photoreactive release of light-responsive ROS responsive drugs LPD in MCF-7 cells for further study on cytotoxicity, cellular uptake and intracellular singlet oxygen (~ 1O 2) levels. The results showed that the particle size of LPD was (169.3 ± 1.2) nm, the PDI was 0.198 ± 0.003, the particle size was uniform and the zeta potential was (-39.8 ± 0.8) mV. LPD has a good photoresponse release characteristic. The DOX release rate reaches 95.5% within 5 min under 730 nm laser light intensity of 300 mW · cm -2. LPD can significantly promote the cellular uptake of DOX, and can produce a large number of cells in the light when ~ 1O_2. Compared with free DOX, IC 50 decreased by 67.9% in LPD and 85.7% decreased in illumination. Therefore, photo-responsive ROS responsive liposomes are promising drug delivery systems.