CAJ | 학술논문

目的研究转铁蛋白(Tf)表面修饰后,载紫杉醇的聚乳酸-羟基乙酸共聚物(PLGA)纳米粒的细胞毒作用及细胞内转运的变化.方法制备2组PLGA纳米粒,1组以聚乙烯醇(PVA)为表面稳定剂(PVA纳米粒) ;1组以PVA为表面稳定剂,并以Tf表面修饰纳米粒(Tf纳米粒),分析2组载紫杉醇的纳米粒对膀胱癌细胞系J-82的细胞毒作用,并研究纳米粒在膀胱癌细胞内的转运.结果紫杉醇溶液、载药PVA纳米粒和载药Tf纳米粒对J-82细胞的50％抑制浓度(IC50)分别为(81±18)、(44±7)和(49±11) ng/ml,后二者明显低于前者(均P＜0.05).J-82细胞对PVA纳米粒和Tf纳米粒的2h摄入水平分别为(89±19)和(76±16) μg/mg细胞蛋白,二者差异无统计学意义(P＞0.05).撤除细胞培养液中纳米粒后,细胞内的纳米粒水平迅速下降,2h后分别有11.3％的PVA纳米粒和18.0％的Tf纳米粒仍滞留于细胞内,此后尽管随着时间的延长,纳米粒的水平维持不变,但是在各个时间点,PVA纳米粒与Tf纳米粒水平的差异均无统计学意义(均P＞0.05).激光共聚焦荧光显微镜发现2种纳米粒均分布于细胞质中.结论 PLGA纳米粒可以显著增强紫杉醇对膀胱癌的抗癌作用,Tf修饰后并未改变纳米粒的细胞毒作用及细胞动力学特点.
목적 연구전철단백(Tf)표면수식후,재자삼순적취유산-간기을산공취물(PLGA)납미립적세포독작용급세포내전운적변화.방법 제비2조PLGA납미립,1조이취을희순(PVA)위표면은정제(PVA납미립) ;1조이PVA위표면은정제,병이Tf표면수식납미립(Tf납미립),분석2조재자삼순적납미립대방광암세포계J-82적세포독작용,병연구납미립재방광암세포내적전운.결과 자삼순용액、재약PVA납미립화재약Tf납미립대J-82세포적50％억제농도(IC50)분별위(81±18)、(44±7)화(49±11) ng/ml,후이자명현저우전자(균P＜0.05).J-82세포대PVA납미립화Tf납미립적2h섭입수평분별위(89±19)화(76±16) μg/mg세포단백,이자차이무통계학의의(P＞0.05).철제세포배양액중납미립후,세포내적납미립수평신속하강,2h후분별유11.3％적PVA납미립화18.0％적Tf납미립잉체류우세포내,차후진관수착시간적연장,납미립적수평유지불변,단시재각개시간점,PVA납미립여Tf납미립수평적차이균무통계학의의(균P＞0.05).격광공취초형광현미경발현2충납미립균분포우세포질중.결론 PLGA납미립가이현저증강자삼순대방광암적항암작용,Tf수식후병미개변납미립적세포독작용급세포동역학특점.
Objective To evaluate the effects of modification of transferrin on cytotoxicity and intracellular delivery of paclitaxel loaded Poly (lactide-co-glycolide) (PLGA) nanoparticle (NPs).Methods PLGA NPs were formulated with microemulsion method,Polyvinyl alcohol (PVA) was used as surfactant (PVA NPs).Transferrin (Tf) was used to modify the NPs (Tf NPs).The cytotoxicity of paclitaxel solution and paclitaxel loaded PVA NPs and Tf NPs were measured in bladder cancer cell line J-82.The intracellular delivery of two kinds of NPs was measured.Results The half maximal inhibitory concentration (IC50) of paclitaxel loaded PVA NPs and Tf NPs was (44 ± 7) and (49 ± 11) ng/ml respectively and significantly lower than that of paclitaxel solution,which was (81 ± 18) ng/ml (both P ＜ 0.05).The uptake of PVA NPs and Tf NPs by J-82 cells after 2 hours was (89 ± 19) μg/mg cellular protein and (76 ± 16)μg/mg cellular protein.The uptake of two kinds of NPs had no significantly difference.The intracellular level of NPs decreased significantly upon the withdrawal of NPs in medium.However,it became stable 2 hours later and 11.3％ PVA NPs and 18.0％ Tf NPs remained.The intracellular level of PVA NPs and Tf NPs had no significantly difference at any timepoint.NPs were distributed in cytoplasm after endosytosis.Conclusions PLGA NPs can significantly improve the anti-neoplasmic effect of paclitaxel on bladder cancer.However,modification of Tf does not change the intracellular dynamics.