Citation: Yiran Tao, Chunlei Dai, Zhaoxiang Xie, Xinru You, Kaiwen Li, Jun Wu, Hai Huang. Redox responsive polymeric nanoparticles enhance the efficacy of cyclin dependent kinase 7 inhibitor for enhanced treatment of prostate cancer[J]. Chinese Chemical Letters, ;2024, 35(8): 109170. doi: 10.1016/j.cclet.2023.109170 shu

Redox responsive polymeric nanoparticles enhance the efficacy of cyclin dependent kinase 7 inhibitor for enhanced treatment of prostate cancer

Yiran Tao ^{a, b, c, 1} ,
Chunlei Dai ^{d, 1} ,
Zhaoxiang Xie ^{a, 1} ,
Xinru You ^e ,
Kaiwen Li ^{a, *,} ,
Jun Wu ^{f, g, h, i, *,} ,
Hai Huang ^{a, f, g, j, *,}

a.
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
b.
Department of Urology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510120, China
c.
Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510120, China
d.
School of Biomedical Engineering, Sun Yat-sen University, Shenzhen 518107, China
e.
Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States
f.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
g.
Department of Urology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan 511518, China
h.
Bioscience and Biomedical Engineering Thrust, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou 511400, China
i.
Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China
j.
Guangdong Provincial Clinical Research Center for Urological Diseases, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China

likw6@mail.sysu.edu.cn

junwuhkust@ust.hk

huangh9@mail.sysu.edu.cn

Received Date: 29 July 2023
Revised Date: 26 September 2023
Accepted Date: 5 October 2023
Available Online: 7 October 2023

Figures(6)

Traditional therapies such as surgery and endocrine therapy no longer meet the clinical needs in prostate cancer treatment, and more effective treatments are urgently required. Recent studies have reported that targeted inhibition of the transcription factor cyclin dependent kinase 7 (CDK7) could effectively suppress prostate cancer progression. However, the toxicity of CDK7 inhibitors such as THZ1 is the main limitation of the clinical application. In this work, we synthesized Cys8E (C8E) nanoparticles (NPs) loaded with THZ1 (C8E@THZ1), a novel GSH-targeting and stimuli-responsive nano-delivery platform, and investigated its anti-tumor potential and biosafety properties. In vitro, C8E@THZ1 potently inhibited the proliferation and promoted the apoptosis of prostate cancer cells. On tumor-bearing mice, C8E@THZ1 inhibited tumors by up to 85%, while the damage of THZ1 to liver function was effectively avoided. These results confirmed that inhibition of CDK7 can effectively block the progression of prostate cancer, and that Cys8E NPs is a highly prospective delivery platform to promote the clinical application of CDK7 inhibitors.
- Prostate cancer,
- Nanoparticles,
- CDK7,
- THZ1,
- THZ1@Cys8E NPs
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