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讲座名称：A Small Molecule Strategy for Targeting Cancer Stem Cells in Hypoxic Microenvironments

讲座人：Jong Seung Kim

讲座时间：4月18日10:00

讲座地点：腾讯会议直播（368993314）

讲座人介绍：

Jong Seung Kim，男，韩国高丽大学教授，韩国科学院院士，韩国化学会副会长，主要从事靶向药物释放系统的开发，生物荧光成像，老年痴呆综合症的检测与治疗方法研究。目前在Nat Rev Mater，Chem Soc Rev，Chem Rev，JACS，Angew. Chem. Int. Ed，Acc Chem Res等80多个国际期刊发表学术论文530余篇，总被引用次数近42000次，H指数达106。自2019年开始，Jong Seung Kim教授连续为全球高被引的前1%科学家。症的检测与治疗方法研究。目前在Nat Rev Mater，Chem Soc Rev，Chem Rev，JACS，Angew. Chem. Int. Ed，Acc Chem Res等80多个国际期刊发表学术论文530余篇，总被引用次数近42000次，H指数达106。自2019年开始，Jong Seung Kim教授连续为全球高被引的前1%科学家。

讲座内容：

Breast cancer consists of heterogenic subpopulations, which determine the prognosis and response to chemotherapy. Among these subpopulations, a very limited number of cancer cells are particularly problematic. These cells, known as breast cancer stem cells (BCSCs), are thought responsible for metastasis and recurrence. They are thus major contributor to the unfavorable outcomes seen for many breast cancer patients. BCSCs are more prevalent in the hypoxic niche. This is an oxygen-deprived environment that is considered crucial to their proliferation, stemness, and self-renewal, but also one that makes BCSCs highly refractory to traditional chemotherapeutic regimens. Here we report a small molecule construct, AzCDF, that allows the therapeutic targeting of BCSCs and which is effective in normally refractory hypoxic tumor environments. A related system, AzNap, has been developed that permits CSC imaging. Several design elements are incorporated into AzCDF, including the CAIX inhibitor, acetazolamide (Az) to promote localization in MDA-MB-231 CSCs, a dimethylnitrothiophene subunit as a hypoxia trigger, and a 3,4-difluorobenzylidene curcumin (CDF) as a readily released therapeutic payload. This allows AzCDF to serve as a hypoxia-liable molecular platform that targets BCSCs selectively that decreases CSC migration, retards tumor growth, and lowers tumorigenesis rates as evidenced by a combination of in vitro and in vivo studies.responsible for metastasis and recurrence. They are thus major contributor to the unfavorable outcomes seen for many breast cancer patients. BCSCs are more prevalent in the hypoxic niche. This is an oxygen-deprived environment that is considered crucial to their proliferation, stemness, and self-renewal, but also one that makes BCSCs highly refractory to traditional chemotherapeutic regimens. Here we report a small molecule construct, AzCDF, that allows the therapeutic targeting of BCSCs and which is effective in normally refractory hypoxic tumor environments. A related system, AzNap, has been developed that permits CSC imaging. Several design elements are incorporated into AzCDF, including the CAIX inhibitor, acetazolamide (Az) to promote localization in MDA-MB-231 CSCs, a dimethylnitrothiophene subunit as a hypoxia trigger, and a 3,4-difluorobenzylidene curcumin (CDF) as a readily released therapeutic payload. This allows AzCDF to serve as a hypoxia-liable molecular platform that targets BCSCs selectively that decreases CSC migration, retards tumor growth, and lowers tumorigenesis rates as evidenced by a combination of in vitro and in vivo studies.

主办单位：生命科学技术学院