文献：Biodegradable Quantum Composites for Synergistic Photothermal Therapy and

Copper-Enhanced Chemotherapy

文献链接：https://pubs.acs.org/doi/10.1021/acsami.0c14636

作者：Han-Xiao Tang,Chen-Guang Liu, Jian-Ting Zhang, Xiang Zheng, Da-Yun Yang, Ranjith

Kumar Kankala, Shi-Bin Wang,and Ai-Zheng Chen

相关产品：SH-PEG5000-FITC 巯基-聚乙二醇5000-荧光素

原文摘要：In recent times, the combination therapy has garnered enormous interest owing to its great potential in clinical research. It has been reported that disulfiram (DSF), a clinical anti-alcoholism drug, could be degraded to diethyldithiocarbamate (DDTC) in vivo and subsequently resulting in the copper-DDTC complex (Cu(DDTC)2) towards ablating cancer cells. In addition, the ultra-small copper sulfide nanodots (CuS NDs) have shown great potential in cancer treatment because of their excellent photothermal and photodynamic therapeutic efficiency. Herein, by taking advantage of the interactions between CuS and DDTC, a new multi-functional nanoplatform, DDTC-loaded CuS (CuS-DDTC) NDs, is successfully fabricated, leading to the achievement of the synergistic effect of photothermal and copper enhanced chemotherapy. All experimental results verified promising synergistic therapeutic effects. Moreover, in vivo biocompatibility and metabolism experiments displayed that the CuS-DDTC NDs could be quickly excreted from the body with no apparent toxicity signs. Together, our findings indicated the superior synergistic therapeutic effect of photothermal and copper enhanced chemotherapy, providing a promising anti-cancer strategy based on CuS-DDTC NDs drug delivery system.

SH - PEG5000 - FITC 是一种多功能的生物活性聚合物。PEG5000 可增加整体的亲水性与生物相容性，减少在生物体内的非特异性吸附。SH（巯基）基团具有很高的化学反应活性，能够与含有马来酰亚胺、乙烯基等基团的生物分子发生特异性反应，实现生物分子的标记与连接。而 FITC 则作为一种常用的荧光标记物，在生物成像领域发挥关键作用，可用于追踪生物分子在细胞内或生物体内的分布、迁移与相互作用等情况，在生物研究、化合物递送系统监测等方面有着应用价值。 双硫仑（DSF）在体内可被降解为二乙基二硫代氨基甲酸酯（DDTC），随后导致铜-DDTC复合物（Cu（DDTC）2）消融cancer细胞。基于此该文献制备SH-PEG5000-FITC标记的CuS-DDTC 纳米点。过程如下：

图：CuS-DDTC纳米点的合成合成的示意图

硫化铜纳米点的合成

简单地说，将CuCl2·2H2o和PVP K15加入水中，在剧烈搅拌下将样品加热。然后，将硫化钠溶液混合，搅拌。随后，将得到的硫化铜纳米点洗涤，并在冻干后保存。SH-PEG5000-FITC标记的硫化铜纳米点（SH-PEG5000-FITC-CuS NDs）制备方法如下：sH与硫化铜纳米点溶液反应，样品黑暗搅拌，离心，用超纯水洗涤。

CuS-DDTC 纳米点的合成

为制备CuS-DDTC 纳米点，硫化铜纳米点在DDTC溶液中搅拌。进一步，收集CuS-DDTC的纳米点，用超纯水洗涤以去除游离的DDTC。通过测定在280 nm处上清液中游离DDTC的含量，测定CuS-DDTC纳米点中的DDTC的含量。

图：硫化铜纳米点的透射电镜图像和插图中的直方图显示了硫化铜纳米点的大小分布

结论：利用硫化铜与DDTC的相互作用，成功制备了新型多功能纳米平台DDTC负载硫化铜（CuS-DDTC）纳米点，实现了光热和铜增强Chemotherapy 的协同效应。所有实验结果均证实了良好的协同效果。此外，体内生物相容性和代谢实验表明，SH-PEG5000-FITC参与标记的CuS-DDTC 纳米点可以迅速从体内排出，没有明显的poison性迹象。