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Updated: Jun 24, 2025
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Precise nano-system-based drug delivery and synergistic therapy against androgen receptor-positive triple-negative
Fangyan Gao1, Yueyao Wu2, Runtian Wang1
1Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Abstract:
Targeting androgen receptor (AR) has shown great therapeutic potential in triple-negative breast cancer (TNBC), yet its efficacy remains unsatisfactory. Here, we aimed to identify promising targeted agents that synergize with enzalutamide, a second-generation AR inhibitor, in TNBC. By using a strategy for screening drug combinations based on the Sensitivity Index (SI), we found that MK-8776, a selective checkpoint kinase1 (CHK1) inhibitor, showed favorable synergism with enzalutamide in AR-positive TNBC. The combination of enzalutamide and MK-8776 was found to exert more significant anti-tumor effects in TNBC than the single application of enzalutamide or MK-8776, respectively. Furthermore, a nanoparticle-based on hyaluronic acid (HA)-modified hollow-manganese dioxide (HMnO2), named HMnE&M@H, was established to encapsulate and deliver enzalutamide and MK-8776. This HA-modified nanosystem managed targeted activation via pH/glutathione responsiveness. HMnE&M@H repressed tumor growth more obviously than the simple addition of enzalutamide and MK-8776 without a carrier. Collectively, our study elucidated the synergy of enzalutamide and MK-8776 in TNBC and developed a novel tumor-targeted nano drug delivery system HMnE&M@H, providing a potential therapeutic approach for the treatment of TNBC.
Insights
This study found that combining enzalutamide with MK-8776 synergistically treats androgen receptor-positive triple-negative breast cancer (TNBC). A novel nanoparticle system enhanced this combination therapy
Area of Science:
- Oncology
- Pharmacology
- Nanotechnology
Background:
- Androgen receptor (AR) targeted therapy shows promise for triple-negative breast cancer (TNBC), but efficacy is limited.
- Enzalutamide is a second-generation AR inhibitor.
- Identifying synergistic agents with enzalutamide is crucial for improving TNBC treatment.
Purpose of the Study:
- To discover novel targeted agents that synergize with enzalutamide in AR-positive TNBC.
- To develop and evaluate a targeted nanoparticle drug delivery system for combined enzalutamide and MK-8776 therapy.
Main Methods:
- Screened drug combinations using the Sensitivity Index (SI) to identify synergistic agents with enzalutamide.
- Investigated the anti-tumor effects of enzalutamide and MK-8776 combination in AR-positive TNBC.
- Developed a hyaluronic acid-modified hollow manganese dioxide nanoparticle (HMnE&M@H) for co-delivery of enzalutamide and MK-8776.
Main Results:
- MK-8776, a CHK1 inhibitor, demonstrated significant synergism with enzalutamide in AR-positive TNBC.
- The enzalutamide and MK-8776 combination exhibited superior anti-tumor effects compared to monotherapy.
- The HMnE&M@H nanoparticle system effectively delivered both drugs and showed enhanced tumor growth repression compared to the free drug combination.
Conclusions:
- Enzalutamide and MK-8776 exhibit synergistic anti-tumor activity in AR-positive TNBC.
- A novel HA-modified nanoparticle (HMnE&M@H) provides a promising platform for targeted co-delivery of enzalutamide and MK-8776.
- This combined therapeutic strategy offers a potential new treatment avenue for TNBC.
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