Dendritic Polyglycerol-Conjugated Gold Nanostars for Metabolism Inhibition and Targeted Photothermal Therapy in Breast Cancer Stem Cells

被引:19
|
作者
Pan, Yuanwei [1 ]
Zhou, Suqiong [1 ]
Liu, Chuang [2 ,3 ]
Ma, Xuehua [2 ,3 ]
Xing, Jie [2 ,3 ]
Parshad, Badri [1 ]
Li, Wenzhong [1 ]
Wu, Aiguo [2 ,3 ]
Haag, Rainer [1 ]
机构
[1] Free Univ Berlin, Inst Chem & Biochem, Takustr 3, D-14195 Berlin, Germany
[2] Chinese Acad Sci, Cixi Inst Biomed Engn, CAS Key Lab Magnet Mat & Devices, Ningbo Inst Mat Technol & Engn, Ningbo 315201, Peoples R China
[3] Chinese Acad Sci, Key Lab Addit Mfg Mat Zhejiang Prov, Ningbo Inst Mat Technol & Engn, Ningbo 315201, Peoples R China
关键词
breast cancer stem cells; dendritic polyglycerol; gold nanostars; metabolism inhibition; photothermal therapy; CO-DELIVERY; 3-BROMOPYRUVATE; NANOPLATFORM; CHEMOTHERAPY; DOXORUBICIN; HEXOKINASE; NANORODS; CHEMO;
D O I
10.1002/adhm.202102272
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Breast cancer stem cells (CSCs) are believed to be responsible for tumor initiation, invasion, metastasis, and recurrence, which lead to treatment failure. Thus, developing effective CSC-targeted therapeutic strategies is crucial for enhancing therapeutic efficacy. In this work, GNSs-dPG-3BP, TPP, and HA nanocomposite particles are developed by simultaneously conjugating hexokinase 2 (HK2) inhibitor 3-bromopyruvate (3BP), mitochondrial targeting molecule triphenyl phosphonium (TPP), and CSCs targeting agent hyaluronic acid (HA) onto gold nanostars-dendritic polyglycerol (GNSs-dPG) nanoplatforms for efficient eradication of CSCs. The nanocomposite particles possess good biocompatibility and exhibit superior mitochondrial-bound HK2 binding ability via 3BP to inhibit metabolism, and further induce cellular apoptosis by releasing the cytochrome c. Therefore, it enhanced the therapeutic efficacy of CSCs-specific targeted photothermal therapy (PTT), and achieved a synergistic effect for the eradication of breast CSCs. After administration of the synergistic treatment, the self-renewal of breast CSCs and the stemness gene expression are suppressed, CSC-driven mammosphere formation is diminished, the in vivo tumor growth is effectively inhibited, and CSCs are eradicated. Altogether, GNSs-dPG-3BP, TPP, and HA nanocomposite particles have been developed, which will provide a novel strategy for precise and highly efficient targeted eradication of CSCs.
引用
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页数:16
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