卢光照, 侯成, 张翮, 孙治国, 鲁莹, 钟延强, 邹豪. 光敏活性氧自由基响应脂质体的制备和评价J. 药学学报, 2017,52(12): 1942-1950. doi: 10.16438/j.0513-4870.2017-0864
引用本文: 卢光照, 侯成, 张翮, 孙治国, 鲁莹, 钟延强, 邹豪. 光敏活性氧自由基响应脂质体的制备和评价J. 药学学报, 2017,52(12): 1942-1950. doi: 10.16438/j.0513-4870.2017-0864
LU Guang-zhao, HOU Cheng, ZHANG He, SUN Zhi-guo, LU Ying, ZHONG Yan-qiang, ZOU Hao. Preparation and evaluation of photo-sensitive reactive oxygen species responsive liposomesJ. Acta Pharmaceutica Sinica, 2017,52(12): 1942-1950. doi: 10.16438/j.0513-4870.2017-0864
Citation: LU Guang-zhao, HOU Cheng, ZHANG He, SUN Zhi-guo, LU Ying, ZHONG Yan-qiang, ZOU Hao. Preparation and evaluation of photo-sensitive reactive oxygen species responsive liposomesJ. Acta Pharmaceutica Sinica, 2017,52(12): 1942-1950. doi: 10.16438/j.0513-4870.2017-0864

光敏活性氧自由基响应脂质体的制备和评价

Preparation and evaluation of photo-sensitive reactive oxygen species responsive liposomes

  • 摘要: 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,PdPC(OBu)8与盐酸多柔比星(doxorubicin hydrochloride,DOX)的脂质体liposome loaded with PdPC(OBu)8 and 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,1O2)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)mV。LPD具有良好的光响应释放特性,在730 nm激光以300 mW·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1O2。与游离DOX相比,LPD未光照时IC50下降67.9%,光照时IC50下降85.7%。因此,光敏ROS响应脂质体是具有前景的给药系统。

     

    Abstract: Photo-sensitive reactive oxygen species (ROS) responsive liposomes loaded with 1,4,8,11,15, 18,22,25-octabutoxypalladium phthalocyaninePdPC(OBu)8 and doxorubicin hydrochloride (DOX) (LPD) were prepared by (NH4)2SO4-gradient method. LPD was characterized with transmission electron microscopy (TEM), dynamic light scattering particle size, zeta potentials, photo-sensitive ROS-responsive DOX release behaviors and the serum stability in vitro. LPD cytotoxicity, DOX uptake and singlet oxygen production in MCF-7 cells were evaluated. The results showed that the particle size of LPD was (169.3 ±1.2) nm, PDI of LPD was 0.198 ±0.003 and zeta potentials of LPD was (-39.8 ±0.8) mV. The accumulated release of DOX reached 95.5% in 5 min under 730 nm laser irradiation (300 mW·cm-2). The DOX uptake of liposome was increased and 1O2 was generated. The half inhibition concentration (IC50) of DOX in LPD with irradiation group was decreased by 85.7% and no irradiation group was decreased by 67.9% compared with free DOX group in MCF-7 cells. Therefore, photo-sensitive ROS-responsive liposomes would be a promising drug delivery system for tumor therapy.

     

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