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

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。

Photo-sensitive reactive oxygen species（ROS）responsive liposomes loaded with 1,4,8,11,15,18,22,25-octabutoxypalladium phthalocyanine[Pd PC（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）m V.The accumulated release of DOX reached 95.5%in 5 min under 730 nm laser irradiation（300 m W·cm^（-2））.The DOX uptake of liposome was increased and ~1O2 was generated.The half inhibition concentration（IC（50））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.