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Dendritic Polyglycerol-Conjugated Gold Nanostars for Metabolism Inhibition and Targeted Photothermal Therapy in
Yuanwei Pan1, Suqiong Zhou1, Chuang Liu2
1Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin, 14195, Germany.
Abstract:
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.
Insights
New nanocomposite particles target breast cancer stem cells (CSCs), inhibiting their metabolism and inducing apoptosis. This synergistic approach enhances photothermal therapy, eradicating CSCs and preventing tumor growth for improved breast cancer treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Breast cancer stem cells (CSCs) drive tumor initiation, metastasis, and recurrence, leading to treatment failure.
- Targeting CSCs is crucial for developing effective breast cancer therapies.
- Existing treatments often fail to eradicate CSCs, necessitating novel strategies.
Purpose of the Study:
- To develop novel nanocomposite particles for targeted eradication of breast CSCs.
- To investigate the synergistic effect of combining photothermal therapy with CSC-specific targeting.
- To evaluate the efficacy of the developed nanocomposite particles in inhibiting CSC self-renewal and tumor growth.
Main Methods:
- Conjugation of hexokinase 2 (HK2) inhibitor 3-bromopyruvate (3BP), triphenyl phosphonium (TPP), and hyaluronic acid (HA) onto gold nanostars-dendritic polyglycerol (GNSs-dPG) nanoplatforms.
- Utilizing GNSs-dPG-3BP, TPP, and HA nanocomposite particles for targeted delivery and inhibition of CSC metabolism.
- Employing CSC-specific targeted photothermal therapy (PTT) in combination with the nanocomposite particles.
Main Results:
- The developed nanocomposite particles demonstrated good biocompatibility and enhanced mitochondrial-bound HK2 binding.
- Inhibition of CSC metabolism by 3BP led to cytochrome c release and induced cellular apoptosis.
- The synergistic treatment effectively suppressed CSC self-renewal, stemness gene expression, and mammosphere formation.
- Significant inhibition of in vivo tumor growth and eradication of CSCs were observed.
Conclusions:
- GNSs-dPG-3BP, TPP, and HA nanocomposite particles offer a novel strategy for precise and highly efficient targeted eradication of CSCs.
- The developed platform enhances therapeutic efficacy by combining metabolic inhibition and targeted photothermal therapy.
- This approach holds promise for overcoming treatment resistance and improving outcomes in breast cancer therapy.
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