彭孝军

个人信息Personal Information

教授

博士生导师

硕士生导师

主要任职:中国化学会创始会士、常务理事,中国化工学会会士

性别:男

毕业院校:大连理工大学

学位:博士

所在单位:化工学院

学科:应用化学. 精细化工. 化学生物学

办公地点:大连理工大学西部校区知顺楼F-202#  
http://peng-group.dlut.edu.cn/

联系方式:大连理工大学西部校区知顺楼F-202 辽宁省大连市高新区凌工路2号,大连116024 课题组网址:http://peng-group.dlut.edu.cn/ E-mail: pengxj@dlut.edu.cn

电子邮箱:pengxj@dlut.edu.cn

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Unimolecular Photodynamic O-2-Economizer To Overcome Hypoxia Resistance in Phototherapeutics

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论文类型:期刊论文

发表时间:2021-04-12

发表刊物:JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

卷号:142

期号:11

页面范围:5380-5388

ISSN号:0002-7863

摘要:Tumor hypoxia has proven to be the major bottleneck of photodynamic therapy (PDT) to clinical transformation. Different from traditional O-2 delivery approaches, here we describe an innovative binary photodynamic O-2-economizer (PDOE) tactic to reverse hypoxia-driven resistance by designing a superoxide radical (O-2(center dot-)) generator targeting mitochondria respiration, termed SORgenTAM. This PDOE system is able to block intracellular O-2 consumption and down-regulate HIF-1 alpha expression, which successfully rescues cancer cells from becoming hypoxic and relieves the intrinsic hypoxia burden of tumors in vivo, thereby sparing sufficient endogenous O-2 for the PDT process. Photosensitization mechanism studies demonstrate that SORgenTAM has an ideal intersystem crossing rate and triplet excited state lifetime for generating O-2(center dot-) through type-I photochemistry, and the generated O-2(center dot-) can further trigger a biocascade to reduce the PDT's demand for O-2 in an O-2-recycble manner. Furthermore, SORgenTAM also serves to activate the AMPK metabolism signaling pathway to inhibit cell repair and promote cell death. Consequently, using this two-step O-2-economical strategy, under relatively low light dose irradiation, excellent therapeutic responses toward hypoxic tumors are achieved. This study offers a conceptual while practical paradigm for overcoming the pitfalls of phototherapeutics.