Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai 200237, People's Republic of China.
Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, People's Republic of China.
Int J Nanomedicine. 2019 Aug 27;14:6917-6932. doi: 10.2147/IJN.S213084. eCollection 2019.
To determine whether the use of a mixed polymeric micelle delivery system based on vitamin E succinate (VES)-grafted-chitosan oligosaccharide (CSO)/VES-grafted-chitosan (CS) mixed micelles (VES-g-CSO/VES-g-CS MM) enhances the delivery of C-DMSA, a theranostic fluorescent probe, for Hg detection and detoxification in vitro and in vivo.
Mixed micelles self-assembled from two polymers, VES-g-CSO and VES-g-CS, were used to load C-DMSA and afforded C-DMSA@VES-g-CSO/VES-g-CS MM for cell and in vivo applications. Fluorescence microscopy was used to assess C-DMSA cellular uptake and Hg detection in L929 cells. C-DMSA@VES-g-CSO/VES-g-CS MM was then administered intravenously. Hg detection was assessed by fluorescence microscopy in terms of bio-distribution while detoxification efficacy in Hg-poisoned rat models was evaluated in terms of mercury contents in blood and in liver.
The C-DMSA loaded mixed micelles, C-DMSA@VES-g-CSO/VES-g-CS MM, significantly enhanced cellular uptake and detoxification efficacy of C-DMSA in Hg pretreated human L929 cells. Evidence from the reduction of liver coefficient, mercury contents in liver and blood, alanine transaminase and aspartate transaminase activities in Hg poisoned SD rats treated with the mixed micelles strongly supported that the micelles were effective for Hg detoxification in vivo. Furthermore, ex vivo fluorescence imaging experiments also supported enhanced Hg detection in rat liver.
The mixed polymeric micelle delivery system could significantly enhance cell uptake and efficacy of a theranostic probe for Hg detection and detoxification treatment in vitro and in vivo. Moreover, this nanoparticle drug delivery system could achieve targeted detection and detoxification in liver.
确定基于维生素 E 琥珀酸酯（VES）接枝壳聚糖寡糖（CSO）/VES 接枝壳聚糖（CS）混合胶束（VES-g-CSO/VES-g-CS MM）的混合聚合物胶束递送系统的使用是否增强了治疗性荧光探针 C-DMSA 的递药作用，用于体外和体内的 Hg 检测和解毒。
使用两种聚合物 VES-g-CSO 和 VES-g-CS 自组装混合胶束，负载 C-DMSA 并提供 C-DMSA@VES-g-CSO/VES-g-CS MM 用于细胞和体内应用。荧光显微镜用于评估 L929 细胞中的 C-DMSA 细胞摄取和 Hg 检测。然后，静脉内给予 C-DMSA@VES-g-CSO/VES-g-CS MM。荧光显微镜用于评估生物分布中的 Hg 检测，而用 Hg 中毒大鼠模型评估血液和肝脏中 Hg 含量来评估解毒功效。
负载 C-DMSA 的混合胶束，C-DMSA@VES-g-CSO/VES-g-CS MM，显著增强了 Hg 预处理的人 L929 细胞中 C-DMSA 的细胞摄取和解毒功效。从混合胶束治疗的 Hg 中毒 SD 大鼠的肝脏系数、肝脏和血液中的汞含量、丙氨酸转氨酶和天冬氨酸转氨酶活性降低的证据强烈支持了胶束在体内的有效解毒作用。此外，离体荧光成像实验也支持了大鼠肝脏中 Hg 检测的增强。
混合聚合物胶束递送系统可显著增强治疗性探针的细胞摄取和体内外 Hg 检测和解毒治疗功效。此外，该纳米药物递送系统可以实现肝脏的靶向检测和解毒。
