聚多巴胺包被的非计量铜硫属纳米颗粒用于肿瘤细胞光热-化疗协同作用研究  

Polydopamine-embedded Nonstoichiometric Copper Chalcogenide Nanoparticles for Chemotherapy-Photothermal Synergistic Therapy against Cancer Cells

作　　者：邹鸿雁 郭青娟 黄承志[1,2] ZOU Hong-Yan;GUO Qing-Juan;HUANG Cheng-Zhi(Key Laboratory of Luminescence Analysis and Molecular Sensing,Ministry of Education,College of Pharmaceutical Sciences,Southwest University,Chongqing 400715,China;Key Laboratory of Luminescent and Real-Time Analytical System,Chongqing Science and Technology Bureau,College of Chemistry and Chemical Engineering,Southwest University,Chongqing 400715,China)

机构地区：[1]发光分析与分子传感教育部重点实验室(西南大学),西南大学药学院,重庆400715 [2]发光与实时分析系统重庆市重点实验室,西南大学化学化工学院,重庆400715

出　　处：《分析化学》2021年第7期1228-1236,共9页Chinese Journal of Analytical Chemistry

基　　金：国家自然科学基金项目(Nos.21535006,21705130);重庆市自然基金项目(No.cstc2020jcyj-msxmX0873)资助。

摘　　要：通过合理的设计制备多功能纳米复合材料是当前实现多模式联合肿瘤治疗领域中的研究热点。本研究合成了在近红外区有局域表面等离子吸收(LSPR)的非计量铜硫属纳米颗粒(Cu_(2-x)S_(y)Se_(1-y) NPs),利用聚多巴胺对其进行表面修饰(Cu_(2-x)S_(y)Se_(1-y)@pDA),进一步通过共价结合,负载叶酸(FA)和抗癌药物硼替佐米(Bortezomib,BTZ),制备了FA-Cu_(2-x)S_(y)Se_(1-y)@pDA-BTZ复合纳米材料。研究表明,此复合纳米材料在生物应用最佳的近红外二区窗口呈现有效吸收,光热转化效率可达30.8%。复合材料可通过表面的叶酸靶向过度表达叶酸受体的癌细胞。此外,聚多巴胺的邻苯二酚基团与BTZ通过动态硼酸酯键交联,利用硼酸酯键的pH响应性质,在肿瘤微酸性环境下,BTZ被可控的释放。将上述FA-Cu_(2-x)S_(y)Se_(1-y)@pDA-BTZ复合材料与HepG-2细胞孵育,在1064 nm激光照射下,癌细胞的存活率低于10%,实现了对肿瘤细胞光热-化疗的协同治疗。此外,此纳米材料可作为一种新型暗场散射探针,用于治疗过程中的癌细胞成像监控。结果表明,合成的非计量铜硫属纳米载药复合材料对癌症诊疗有很好的应用前景。Developing multifunctional nanomaterials is a hot topic for the combination therapy of tumor cells.In this work,a distinctive multifunctional composite(FA-Cu_(2-x)S_(y)Se_(1-y)@pDA-BTZ)was fabricated by assembling folic acid(FA)and the anticancer drug bortezomib(BTZ)to the surface of the nonstoichiometric copper chalcogenide nanoparticle(Cu_(2-x)S_(y)Se_(1-y) NPs)with typical local ized surface plasmon resonance(LSPR)in the near-infrared region coated by polydopamine(Cu_(2-x)S_(y)Se_(1-y)@pDA).The FA-Cu_(2-x)S_(y)Se_(1-y)@pDA-BTZ showed a good light harvest in the second near-infrared window for bio-application and the photothermal conversion efficiency could reach 30.8%.FA was attached to the surface of the Cu_(2-x)S_(y)Se_(1-y)@pDA,so that the nanocomplex could be specifically delivered into cancer cells with overexpressed folate receptor.Meanwhile,BTZ could easily bind with Cu_(2-x)S_(y)Se_(1-y)@pDA through the formation of pHresponsive boronate ester bond between boronic acid and catechol groups in polydopamine under weakly alkaline conditions.Under 1064 nm laser irradiation in weakly acidic phosphate buffer,the controlled release of drugs was obtained.Under the laser irradiation(1064 nm),the relative survival rate of the cells was lower than 10%,which could realize the synergistic treatment of photothermal therapy and chemotherapy for tumor cells.The FA-Cu_(2-x)S_(y)Se_(1-y)@pDA-BTZ could be used as a new probe in the dark-field imaging for monitoring the therapy.The above results showed that the synthesized FA-Cu_(2-x)S_(y)Se_(1-y)@pDA-BTZ multifunctional composite had a good application prospect in the diagnosis and treatment of cancer.

关 键 词：非计量铜硫属纳米颗粒 近红外二区 局域表面等离子吸收 光热治疗 暗场成像 

分 类 号：R73-3[医药卫生—肿瘤] TB383.1[医药卫生—临床医学]