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

• Published in: Chinese chemical letters 2024-08, Vol.35 (8), p.109170, Article 109170
• Main Authors: Tao, Yiran, Dai, Chunlei, Xie, Zhaoxiang, You, Xinru, Li, Kaiwen, Wu, Jun, Huang, Hai
• Format: Article
• Language: English
• Subjects: CDK7; Nanoparticles; Prostate cancer; THZ1; THZ1@Cys8E NPs
• ISSN: 1001-8417; 1878-5964
• DOI: 10.1016/j.cclet.2023.109170

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. THZ1 could become a novel therapeutic regimen and meanwhile Cys8E nanoparticles (NPs) might work as an outstanding glutathione (GSH)-targeted nanoplatform that might facilitate the clinical application of THZ1 with less toxicity in the therapeutic regimen of prostate cancer. [Display omitted]