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...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.展开更多
基金supported by the National Key R&D Plan of China(No.2022YFC3602904)the National Natural Science Foundation of China(Nos.81974395,82173036)+11 种基金Guangdong Basic and Applied Basic Research Foundation(No.2019A1515011437)International Science and Technology Cooperation Project Plan of Guangdong Province(No.2021A0505030085)Sun Yat-Sen University Clinical Research 5010 Program(No.2019005)Beijing Bethune Charitable Foundation(No.mnzl202001)Guangzhou Science and Technology Key R&D Project(No.202206010117)Beijing CSCO Clinical Oncology Research Foundation(Nos.Ytongshu2021/ms-0162,Y-MSDZD2022-0760)Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation(No.2020B1212060018OF006)Guangdong Provincial Clinical Research Center for Urological Diseases(No.2020B1111170006)supported by the National Natural Science Foundation of China(Nos.52173150,51973243)supported by the National Natural Science Foundation of China(No.82173088)Natural Science Foundation of Guangdong(No.2022A1515012383)the Guangzhou Science and Technology Fund(No.A202201011299)
文摘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.
