Dendritic Polyglycerol-Conjugated Gold Nanostars for Metabolism Inhibition and Targeted Photothermal Therapy in Breast Cancer Stem Cells
| Autor: | Yuanwei Pan, Suqiong Zhou, Chuang Liu, Xuehua Ma, Jie Xing, Badri Parshad, Wenzhong Li, Aiguo Wu, Rainer Haag |
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| Rok vydání: | 2022 |
| Předmět: |
Glycerol
breast cancer stem cells photothermal therapy Polymers Biomedical Engineering Pharmaceutical Science metabolism inhibition Breast Neoplasms 500 Naturwissenschaften und Mathematik::570 Biowissenschaften Biologie::570 Biowissenschaften Biologie Biomaterials Cell Line Tumor Neoplastic Stem Cells Humans Female gold nanostars Gold Hyaluronic Acid dendritic polyglycerol |
| DOI: | 10.17169/refubium-33603 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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