负载表柔比星的氟化白蛋白纳米粒的构建及其在膀胱尿路上皮渗透潜能的研究  

Establishment of fluorinated albumin nanoparticles loaded with epirubicin and its osmotic potential in urothelium

作　　者：杨佳健 徐安安 沈罡 浦金贤 缪志俊 Yang Jiajian;Xu Anan;Shen Gang;Pu Jinxian;Miao Zhijun(Department of Urology,The Fourth Affiliated Hospital of Soochow University(Suzhou Dushu Lake Hospital),Suzhou 215123,China;Jiangsu Key Laboratory of Neuropsychiatric Diseases,College of Pharmaceutical Sciences,Soochow University,Suzhou 215123,China)

机构地区：[1]苏州大学附属第四医院(苏州市独墅湖医院)泌尿外科,苏州215123 [2]苏州大学药学院江苏省神经精神疾病重点实验室,苏州215123

出　　处：《中华泌尿外科杂志》2025年第3期219-225,共7页Chinese Journal of Urology

摘　　要：目的探讨负载表柔比星(EPI)的氟化人血白蛋白(F-HSA)纳米粒EPI@F-HSA的构建及其在C57雌性小鼠膀胱灌注后尿路上皮渗透的潜能。方法本研究于2023年1-12月进行。基于生物矿化原理以EPI和人血白蛋白(HSA)为原料合成负载EPI的白蛋白纳米粒EPI@HSA,进一步通过酰胺反应制得EPI@F-HSA。采用动态光散射及电位分析仪检测两者的分子表征,绘制EPI在0.25、0.5、1、2、4、8、12、24、48 h时的体外释放曲线。通过MTT实验测定EPI@HSA和EPI@F-HSA纳米粒对小鼠膀胱癌细胞系MB49活性的抑制作用。用共聚焦显微镜记录药物灌注后雌鼠膀胱切片中EPI的荧光分布,并采用图基检验法检测荧光密度差异以反映EPI@F-HSA纳米粒对尿路上皮的渗透作用。结果EPI@HSA和EPI@F-HSA纳米粒的平均水合粒径分别为28.2 nm和32.7 nm,多分散系数为0.102和0.154。在pH值为5.0的缓冲液中,12 h内EPI@HSA和EPI@F-HSA纳米粒中的EPI累计释放量分别为60.5%和58.2%;在pH值为7.4的缓冲液中,12 h内EPI@HSA和EPI@F-HSA纳米粒中的EPI释放量分别为32.8%和27.1%。EPI@HSA和EPI@F-HSA纳米粒对MB49膀胱癌细胞的半数抑制浓度分别为1.848μmol/L和1.650μmol/L。游离EPI、EPI@HSA和EPI@F-HSA纳米粒经灌注后膀胱壁中的EPI荧光强度分别为2.63±0.43、3.22±0.20和8.71±0.70,EPI@F-HSA的荧光强度显著高于EPI@HSA(P<0.01)和游离EPI(P<0.01)。结论制备的EPI@F-HSA纳米粒粒径均一且稳定性良好,能显著抑制肿瘤细胞活性并增强EPI渗透膀胱黏膜的能力,具有提升抗肿瘤疗效的潜能,有望成为一种新型的靶向膀胱癌的药物传送系统。ObjectiveTo investigate the construction of fluorinated human serum albumin(F-HSA)nanoparticles loaded with epirubicin(EPI)EPI@F-HSA and its potential in urothelium penetration after bladder perfusion in female C57 mice.MethodsFrom January 2023 to December 2023,HSA and EPI were selected as raw materials to synthesize albumin nanoparticles loaded with EPI(EPI@HSA)based on the principles of biomineralization.EPI@F-HSA was synthesized through an amide reaction.The molecular descriptor of hydrated particles were measured by dynamic light scattering and potentiometric analyzer,and the release curve of EPI in vitro was plotted at 0.25,0.5,1,2,4,8,12,24 and 48 h.The inhibitory effect of EPI@HSA and EPI@F-HSA nanoparticles on MB49 tumor cell activity was determined by MTT assay.The fluorescence distribution of EPI in mouse bladder sections after drug infusion was recorded by confocal microscope and the difference of fluorescence density of EPI was examined by Tukey post-hoc test to reflect the urothelium permeability.ResultsThe average hydrated particle sizes of EPI@HSA and EPI@F-HSA were 28.2 nm and 32.7 nm,respectively,and the polydispersity index(PDI)were 0.102 and 0.154.The cumulative EPI release of EPI@HSA and EPI@F-HSA nanoparticles within 12 h were 60.5%and 58.2%respectively in pH 5.0 buffer solution,and were 32.8%and 27.1%in pH 7.4 buffer solution.The median inhibitory concentrations of EPI@HSA and EPI@F-HSA nanoparticles on MB49 bladder cancer cells were 1.848μmol/L and 1.650μmol/L respectively.After perfusion with EPI,EPI@HSA,and EPI@F-HSA,the fluorescence intensities of EPI in the bladder wall were 2.63±0.43,3.22±0.20 and 8.71±0.70,respectively,and the EPI fluorescence intensity of EPI@F-HSA was significantly higher than that of EPI@HSA(P<0.01)and free EPI(P<0.01).ConclusionsThe fluorinated albumin nanoparticles had uniform particle size,good stability,significant inhibition of tumor cell activity and osmotic potential in urothelium,which had the potential to improve the anti-tumor efficacy and were expec

关 键 词：膀胱肿瘤 癌 氟化物 白蛋白 纳米技术 表柔比星 深部渗透 

分 类 号：R737.14[医药卫生—肿瘤]