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Sequential Responsive Multifunctional Nanomicelle Effectuates Collective Elimination of Breast Cancer and Cancer Stem
Xing Wang1, Yuqi Tang1, Li Yang1
1School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, P. R. China.
Abstract:
Designing effective multifunctional nanodrugs to achieve multimodal treatment of tumors is an ideal choice to improve the poor clinical outcomes of current anti-tumor therapies. Here, a multifunctional nanomicelle DC@H loaded with sarcoma kinase and cyclooxygenase-2 protein dual target inhibitor DI02 is designed and prepared, which is sequentially catalyzed by carboxylesterase and glutathione for reduction, and strengthens the inhibition of cancer stem cell (CSC) related protein STAT3. The camptothecin carried by the DC@H ensures the effectiveness of chemotherapy. Ultimately, DC@H precisely releases and achieves effective inhibition of xenograft tumors based on the combination of chemotherapy, targeted therapy, and chemodynamic therapy, with a tumor inhibition rate of up to 90.89% in BALB/c nude mice. Research on lung metastasis proves that the CSC inhibitory characteristic of DC@H is a direct cause of the elimination of tumor metastatic nodules. There is no doubt that the multifunctional nano drug DC@H, which effectuates the collective elimination of breast cancer and cancer stem cells, provides a promising direction for achieving complete tumor cure in clinical practice.
Insights
A novel multifunctional nanomicelle, DC@H, combines chemotherapy, targeted therapy, and chemodynamic therapy to effectively inhibit breast cancer and cancer stem cells (CSCs), achieving a 90.89% tumor inhibition rate.
Area of Science:
- Oncology
- Nanotechnology
- Pharmacology
Background:
- Current anti-tumor therapies have poor clinical outcomes.
- Multimodal treatment using multifunctional nanodrugs is ideal for improving outcomes.
- Cancer stem cells (CSCs) contribute to tumor recurrence and metastasis.
Purpose of the Study:
- To design and prepare a multifunctional nanomicelle, DC@H, for combined anti-cancer therapies.
- To evaluate the efficacy of DC@H in inhibiting tumor growth and metastasis.
- To investigate the role of DC@H in inhibiting cancer stem cells (CSCs).
Main Methods:
- A nanomicelle (DC@H) was engineered, co-delivering a dual-target inhibitor (DI02) and camptothecin.
- DC@H was designed for sequential catalysis by carboxylesterase and glutathione, releasing therapeutic agents.
- In vivo studies in BALB/c nude mice assessed tumor inhibition and lung metastasis.
- The inhibition of STAT3, a CSC-related protein, was investigated.
Main Results:
- DC@H demonstrated precise drug release and effective inhibition of xenograft tumors.
- The nanodrug achieved a tumor inhibition rate of up to 90.89%.
- DC@H significantly reduced lung metastasis by inhibiting CSCs, eliminating metastatic nodules.
Conclusions:
- The multifunctional nanodrug DC@H offers a promising strategy for complete tumor eradication.
- DC@H effectively targets both primary tumors and cancer stem cells.
- This approach combines chemotherapy, targeted therapy, and chemodynamic therapy for superior anti-cancer effects.
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