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

引用

Chinese Chemical Letters 2024年第8期35卷 443-448页

作者： Yiran Tao Chunlei Dai Zhaoxiang Xie Xinru You Kaiwen Li Jun Wu Hai Huang Department of Urology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Department of Urology The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510120China Biomedical Innovation Center The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510120China School of Biomedical engineering Sun Yat-sen UniversityShenzhen 518107China Center for Nanomedicine and Department of Anesthesiology Brigham and Women’s HospitalHarvard Medical SchoolBostonMA 02115United States Guangdong Provincial Key Laboratory of Malignant Tumor epigenetics and Gene Regulation Sun Yat-sen Memorial HospitalSun Yat-Sen UniversityGuangzhou 510120China Department of Urology The Sixth Affiliated Hospital of Guangzhou Medical UniversityQingyuan People’s HospitalQingyuan 511518China Bioscience and Biomedical engineering Thrust The Hong Kong University of Science and Technology(Guangzhou)Guangzhou 511400China Division of Life Science The Hong Kong University of Science and TechnologyHong KongChina Guangdong Provincial Clinical Research Center for Urological Diseases Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China

Traditional therapies such as surgery and endocrine therapy no longer meet the clinical needs in prostate cancer treatment,and more effective treatments are urgently *** studies have reported that targeted inhibition of the transcription factor cyclin dependent kinase 7(CDK7)could effectively suppress prostate cancer ***,the toxicity of CDK7 inhibitors such as thz1 is the main limitation of the clinical *** 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 *** vitro,C8e@thz1 potently inhibited the proliferation and promoted the apoptosis of prostate cancer *** tumor-bearing mice,C8e@thz1 inhibited tumors by up to 85%,while the damage of thz1 to liver function was effectively *** 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.

关键词： Prostate cancer Nanoparticles CDK7 thz1 thz1@cys8e nps

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