Peptidomimetic-liganded gold nanoclusters for controlled iron delivery and synergistic suppression of tumor growth  

作　　者：Xiqi Ma Duo Cai Zhixiong Zhang Qi Dai Xinyu Li Biao Yu Baosheng Ge Shihai Liu Xiaojuan Wang Fang Huang 

机构地区：[1]College of Chemical Engineering,State Key Laboratory of Heavy Oil Processing,China University of Petroleum(East China),Qingdao 266580,China [2]Medical Animal Laboratory,Affiliated Hospital of Qingdao University,Qingdao 266500,China

出　　处：《Nano Research》2023年第10期12066-12075,共10页纳米研究（英文版）

基　　金：the National Natural Science Foundation of China(Nos.22177133,42061134020,and 32070380);the Natural Science Foundation of Shandong Province(Nos.ZR2019ZD17 and ZR2021MH022);the Qingdao Municipal People’s Livelihood Science and Technology Project(No.17-3-3-76-nsh);the Graduate Innovative Engineering Funding project of UPC(No.YCX2020041).

摘　　要：A novel peptidomimetic-liganded gold nanocluster(CDp-AuNC)is proposed for the synergistic suppression of tumor growth.Taking advantages of the multi-capabilities offered by the surface ligands,including iron chelation,glutathione peroxidases-1(GPx-1)binding,and tumor cells recognition,CDp-AuNCs are able to function as the nanocarriers to deliver iron in a controlled manner for the ferroptosis therapy and as the inhibitors for GPx-1 to induce the apoptosis of tumor cells.The Fe2+@CDp-AuNC nanocomplexes are fabricated through a facile self-assembly method.The experimental data verify that the nanocomplexes are internalized specifically by tumor cells with high efficiency.The acidic microenvironment in endosomes triggers the collapse of the nanocomplexes and thereby releases Fe2+to induce ferroptosis and CDp-AuNCs to inhibit the enzyme activity of GPx-1.Benefiting from the H_(2)O_(2)-depleted pathway inhibition and ferroptosis acceleration,the intracellular reactive oxygen species(ROS)level could be enhanced significantly.As a consequence,the apoptosis/ferroptosis of 4T1 cells as well as the tumor elimination in vivo are observed after treatment with the Fe2+@CDp-AuNC nanocomplexes at a relatively low dose.The facile iron loading method,simple construction procedure,and outstanding tumor suppression performance,provide CDp-AuNCs great application promise.More importantly,the strategy of peptidomimetic ligands design provides a transferable approach to building multifunctional nanomaterials.

关 键 词：SELF-ASSEMBLY drug delivery ferroptosis PEPTIDOMIMETICS gold nanocluster 

分 类 号：TB383[一般工业技术—材料科学与工程]