Low-density lipoprotein receptor-related protein 1(LRP1,also known as CD91),a multifunctional endocytic and cell signaling receptor,is widely expressed on the surface of multiple cell types such as hepatocytes,fibrobl...Low-density lipoprotein receptor-related protein 1(LRP1,also known as CD91),a multifunctional endocytic and cell signaling receptor,is widely expressed on the surface of multiple cell types such as hepatocytes,fibroblasts,neurons,astrocytes,macrophages,smooth muscle cells,and malignant cells.Emerging in vitro and in vivo evidence demonstrates that LRP1 is critically involved in many processes that drive tumorigenesis and tumor progression.For example,LRP1 not only promotes tumor cell migration and invasion by regulating matrix metalloproteinase(MMP)-2and MMP-9 expression and functions but also inhibits cell apoptosis by regulating the insulin receptor,the serine/threonine protein kinase signaling pathway,and the expression of Caspase-3.LRPI-mediated phosphorylation of the extracellular signal-regulated kinase pathway and c-jun N-terminal kinase are also involved in tumor cell proliferation and invasion.In addition,LRP1 has been shown to be down-regulated by microRNA-205 and methylation of LRP1CpG islands.Furthermore,a novel fusion gene,LRP1-SNRNP25,promotes osteosarcoma cell invasion and migration.Only by understanding the mechanisms of these effects can we develop novel diagnostic and therapeutic strategies for cancers mediated by LRP1.展开更多
The recent development of the two-photon technique offers a unique opportunity to improve the depth of imaging and treatment in photodynamic therapy(PDT).Herein,we designed a fluorescence resonance energy transfer(FRE...The recent development of the two-photon technique offers a unique opportunity to improve the depth of imaging and treatment in photodynamic therapy(PDT).Herein,we designed a fluorescence resonance energy transfer(FRET)based AceDAN-porphyrin(Zn)dyad for two-photon excited fluorescence imaging and PDT of cancer cells simultaneously,in which the AceDAN moiety was selected as the two-photon absorption donor and the porphyrin(Zn)moiety served as the energy acceptor.Upon one-photon or two-photon excitation,the excited state energy of the AceDAN donor was transferred to the porphyrin(Zn)acceptor with high efficiency(η_(EET)=98%),where red fluorescence and singlet oxygen were generated.Dyad 1 exhibited high photocytotoxicity towards A549 cells(IC_(50)=4.3μM)with rapid cellular uptake while displaying low dark-cytotoxicity.Furthermore,by combining the advantages of two-photon excitation with a porphyrin(Zn)photosensitizer,the AceDAN-porphyrin(Zn)dyad has been successfully applied to A549 cells for imaging and photodynamic therapy under two-photon laser irradiation.展开更多
基金the National Natural Science Foundation of China(81372872 to J.Yang,81402215 to X.Du,and 81320108022 to K.Chen)funds from the University Cancer Foundation via the Sister Institution Network Fund at the Tianjin Medical University Cancer Institute and Hospital,Fudan University Shanghai Cancer Center,and University of Texas MD Anderson Cancer Centersupported by the program for Innovative Research Team in University in China(IRT1076 to K.Chen)
文摘Low-density lipoprotein receptor-related protein 1(LRP1,also known as CD91),a multifunctional endocytic and cell signaling receptor,is widely expressed on the surface of multiple cell types such as hepatocytes,fibroblasts,neurons,astrocytes,macrophages,smooth muscle cells,and malignant cells.Emerging in vitro and in vivo evidence demonstrates that LRP1 is critically involved in many processes that drive tumorigenesis and tumor progression.For example,LRP1 not only promotes tumor cell migration and invasion by regulating matrix metalloproteinase(MMP)-2and MMP-9 expression and functions but also inhibits cell apoptosis by regulating the insulin receptor,the serine/threonine protein kinase signaling pathway,and the expression of Caspase-3.LRPI-mediated phosphorylation of the extracellular signal-regulated kinase pathway and c-jun N-terminal kinase are also involved in tumor cell proliferation and invasion.In addition,LRP1 has been shown to be down-regulated by microRNA-205 and methylation of LRP1CpG islands.Furthermore,a novel fusion gene,LRP1-SNRNP25,promotes osteosarcoma cell invasion and migration.Only by understanding the mechanisms of these effects can we develop novel diagnostic and therapeutic strategies for cancers mediated by LRP1.
基金National Natural Science Foundation of China(21471015 and 21631003)Beijing Natural Science FoundationFundamental Research Funds for the Central Universities。
文摘The recent development of the two-photon technique offers a unique opportunity to improve the depth of imaging and treatment in photodynamic therapy(PDT).Herein,we designed a fluorescence resonance energy transfer(FRET)based AceDAN-porphyrin(Zn)dyad for two-photon excited fluorescence imaging and PDT of cancer cells simultaneously,in which the AceDAN moiety was selected as the two-photon absorption donor and the porphyrin(Zn)moiety served as the energy acceptor.Upon one-photon or two-photon excitation,the excited state energy of the AceDAN donor was transferred to the porphyrin(Zn)acceptor with high efficiency(η_(EET)=98%),where red fluorescence and singlet oxygen were generated.Dyad 1 exhibited high photocytotoxicity towards A549 cells(IC_(50)=4.3μM)with rapid cellular uptake while displaying low dark-cytotoxicity.Furthermore,by combining the advantages of two-photon excitation with a porphyrin(Zn)photosensitizer,the AceDAN-porphyrin(Zn)dyad has been successfully applied to A549 cells for imaging and photodynamic therapy under two-photon laser irradiation.
