首页|Precise nano-system-based drug delivery and synergistic therapy against androgen receptor-positive triple-negative breast cancer

Precise nano-system-based drug delivery and synergistic therapy against androgen receptor-positive triple-negative breast cancer

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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 tar-geted 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.

Triple-negative breast cancerAndrogen receptorCheckpoint kinase 1EnzalutamideMK-8776SynergyHMnO2Nanodrug delivery system

Fangyan Gao、Yueyao Wu、Runtian Wang、Yuhui Yao、Yiqiu Liu、Lingling Fan、Jingtong Xu、Jian Zhang、Xin Han、Xiaoxiang Guan

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Department of Oncology,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization,School of Medicine &Holistic Integrative Medicine,Nanjing University of Chinese Medicine,Nanjing 210023,China

Department of Oncology,the Second Hospital of Nanjing,Nanjing University of Chinese Medicine,Nanjing 210023,China

Department of Medical Oncology,Fudan University Shanghai Cancer Center,Shanghai 200032,China

Jiangsu Key Lab of Cancer Biomarkers,Prevention and Treatment,Collaborative Innovation Center for Cancer Personalized Medicine,Nanjing Medical University,Nanjing 211166,China

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Key INTERNATIONAL COOPERATION of the National Natural Science Foundation of ChinaKey Foundation for Social Development Project of the Jiangsu Province,China

81920108029BE2021741

2024

10.1016/j.apsb.2024.03.012

药学学报(英文版)

药学学报(英文版)

CSTPCD
ISSN：
年,卷(期)：2024.14(6)
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