基于乳腺癌化疗-光动力联合治疗的负载紫杉醇白蛋白纳米给药系统的制备及其体外评价  

Preparation and in vitro evaluation of human serum albumin nano-drug delivery system loaded with paclitaxel for chemo-photodynamic combined therapy of breast cancer

作　　者：亓文霞 王胜兰 杨桁 高科 王云腾 孙钰迪 赵峰[1] 张加余 张静[1] QI Wen-xia;WANG Sheng-lan;YANG Heng;GAO Ke;WANG Yun-teng;SUN Yu-di;ZHAO Feng;ZHANG Jia-yu;ZHANG Jing(Key Laboratory of Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine of China,School of Pharmacy,Binzhou Medical University,Yantai 264003,China)

机构地区：[1]滨州医学院药学院国家中医药管理局方剂效应与临床评价重点研究室,山东烟台264003

出　　处：《中草药》2022年第4期993-1003,共11页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81703391);山东省自然科学基金重点项目(ZR2020KB015);山东省自然科学基金项目(ZR2021MC091);山东省青创人才引育团队—中药复杂体系作用模式解析创新研究团队项目(10073004);山东省大学生创新创业训练计划(S202010440063);山东省大学生创新创业训练计划(S202110440055)。

摘　　要：目的以光敏剂二氢卟吩e6(chlorin e6,Ce6)修饰人血清白蛋白(human serum albumin,HSA)为载体,负载抗肿瘤药物紫杉醇(paclitaxel,PTX)后构建纳米给药系统PTX@HSA-Ce6,以实现肿瘤“化疗-光动力”联合治疗,改善乳腺癌治疗效果。方法共价结合法制备HSA-Ce6,红外光谱、紫外-可见吸收光谱和荧光光谱进行表征;自组装法制备载药纳米粒PTX@HSA-Ce6,对其粒径分布、表面ζ电位、形貌及稳定性进行表征,研究其药物负载和释放行为;利用乳腺癌MCF-7细胞模型考察PTX@HSA-Ce6的活性氧产生、细胞摄取及体外抗肿瘤效果。结果当HSA与Ce6投料比为1:10时,制备得到的PTX@HSA-Ce6呈规整的球形,平均粒径为(147.4±0.9)nm,ζ电位为(—15.2±0.6)mV,具有良好的稳定性。PTX@HSA-Ce6可有效负载紫杉醇,具有pH敏感性药物缓释效果。PTX@HSA-Ce6可被MCF-7细胞快速、持续摄取,激光照射下可在胞内产生活性氧,与紫杉醇发挥联合抗肿瘤作用。结论PTX@HSA-Ce6可实现对Ce6和紫杉醇的共载和胞内递送,发挥化疗-光动力治疗联合抗肿瘤作用,有利于改善乳腺癌的治疗效果。Objective A paclitaxel(PTX)-loaded nano-drug delivery system based on chlorin e6(Ce6)-conjugated human serum albumin(HSA)was prepared for chemo-photodynamic combined therapy of breast cancer to improve therapeutic efficacy.Methods HSA-Ce6 conjugates were prepared by covalent coupling method,and their FT-IR spectra,UV-vis absorption spectra and fluorescence spectra were analyzed.Paclitaxel-loaded HSA-Ce6 nanoparticles(PTX@HSA-Ce6)were prepared by self-assembling and their particle distribution,ζpotential,morphology and stability were characterized.The drug loading and release profiles of PTX@HSA-Ce6 were examined.The in vitro intracellular reactive oxygen species(ROS)generation,cellular uptake and cytotoxicity of PTX@HSA-Ce6 were evaluated on human breast cancer MCF-7 cells.Results PTX@HSA-Ce6 prepared with a HSA/Ce6 molar ratio of 1:10 displayed uniformly spherical shape and good stability with a mean particle size of(147.4±0.9)nm andζpotential of(−15.2±0.6)mV.PTX@HSA-Ce6 could efficiently load paclitaxel and showed sustained drug release behaviors with pH-sensitivity.PTX@HSA-Ce6 could be rapidly and continuously taken up by MCF-7 cells,and generated intracellular ROS after laser irradiation.MTT assay indicated that PTX@HSA-Ce6 exhibited significantly higher inhibitory effect on the in vitro proliferation of MCF-7 cells compared with the single treatment of paclitaxel or HSA-Ce6.Conclusion PTX@HSA-Ce6 could facilitate the co-loading and intracellular delivery of Ce6 and paclitaxel,therefore enhance the therapeutic efficacy of breast cancer by chemo-photodynamic combined therapy.

关 键 词：紫杉醇 二氢卟吩e6 人血清白蛋白 纳米给药系统 化疗 光动力治疗 乳腺癌 共价结合法 自组装法 

分 类 号：R283.6[医药卫生—中药学]