期刊
ADVANCED HEALTHCARE MATERIALS
卷 11, 期 8, 页码 -出版社
WILEY
DOI: 10.1002/adhm.202102272
关键词
breast cancer stem cells; dendritic polyglycerol; gold nanostars; metabolism inhibition; photothermal therapy
资金
- China Scholarship Council
In this study, a method for efficient eradication of CSCs was developed by conjugating HK2 inhibitor, mitochondrial targeting molecule, and CSCs targeting agent onto a nanoplatform. The nanocomposite particles showed good biocompatibility and enhanced therapeutic efficacy by inhibiting metabolism and inducing cellular apoptosis. The treatment successfully suppressed CSC self-renewal and tumor growth, achieving eradication of CSCs.
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.
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