文献：Enhancing Antitumor Efficacy by Simultaneous ATP-Responsive Chemodrug Release and Cancer Cell Sensitization Based on a Smart Nanoagent

文献链接：https://onlinelibrary.wiley.com/doi/full/10.1002/advs.201801201

作者：Xiao-Rong Song, Shi-Hua Li, Hanhan Guo, Wenwu You, Datao Tu, Juan Li, Chun-Hua Lu, Huang-Hao Yang, and Xueyuan Chen

相关产品：DSPE-PEG，Mw2000（二硬脂酰基磷脂酰乙醇胺-聚乙二醇）

原文摘要：

   The exploitation of smart nanoagents based drug delivery systems (DDSs) has proven to be a promising strategy for fighting cancers. Hitherto, such nanoagents still face challenges associated with their complicated synthesis, insufficient drug release in tumors, and low cancer cell chemosensitivity. Here, the engineering of an adenosine triphosphate (ATP)-activatable nanoagent is demonstrated based on self-assembled quantum dots-phenolic nanoclusters to circumvent such challenges. The smart nanoagent constructed through a one-step assembly not only has high drug loading and low cytotoxicity to normal cells, but also enables ATP-activated disassembly and controlled drug delivery in cancer cells. Particularly, the nanoagent can induce cell ATP depletion and increase cell chemosensitivity for significantly enhanced cancer chemotherapy. Systematic in vitro and in vivo studies further reveal the capabilities of the nanoagent for intracellular ATP imaging, high tumor accumulation, and eventual body clearance. As a result, the presented multifunctional smart nanoagent shows enhanced antitumor efficacy by simultaneous ATP-responsive chemodrug release and cancer cell sensitization. These findings offer new insights toward the design of smart nanoagents for improved cancer therapeutics.

DSPE-PEG是一种磷脂-聚乙二醇共轭物，可作为化合物载体，用于靶向传递。通过改变PEG的分子量或对其进行化学修饰，可以调节DSPE-PEG的物理化学性质，从而优化化合物的装载、释放和靶向性能。通过DSPE-PEG组装构建的纳米载体——量子点@单宁酸 纳米团簇智能不仅具有较高的化合物负载能力和对正常细胞的低细胞poison性，而且，该纳米载体能够诱导细胞ATP耗竭，从而提升效果。

图：QDs@TA-PEG/DOX增强效果示意图

量子点@单宁酸 酚醛树脂纳米团簇QDs@TA NCs的制备：将TA水溶液与环己烷QDs溶液混合，然后搅拌并超声处理。分层后，收集得到的水相溶液。离心，用乙醇和水洗涤后，获得QDs@TA NCs，4°C保存以供进一步使用。对于DSPE-PEG修饰，将DSPE-PEG（Mw2000,）与NCs搅拌过夜，离心洗涤得到QDs@TA-PEG NCs。

化合物在QDs@TA-pegnc中载药释放：将TA和DOX水溶液与量子点环己烷溶液混合，搅拌超声。NCs形成后上药，将QDs@TA NCs与DOX水溶液搅拌，得到QDs@TA-PEG/ DOX。

图：QDs@TAnc的组装和atp激活的拆卸示意图

结论：

DSPE-PEG可以作为纳米粒表面的修饰剂制备得到QDs@TA NCs，通过改变纳米粒的表面性质，提高其生物相容性、稳定性和靶向性。由DSPE-PEG合成的QDs@TA-PEG/DOX智能纳米化合物，通过结合cancer特异性控制化合物传递和cancer cell致敏，以改善抗tumour效果。该纳米剂具有高载药能力，可以通过ATP激活明显分解，使ATP激活的控制化合物在cancer细胞中释放，降低对正常细胞的poison性。