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,ζ potential, 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 and ζ potential 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.

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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）