Development of tumor microenvironment responsive and multi-mode imaging guided photodynamic therapy(PDT)is highly desired.Herein,we report a MnO_(2)-coated and redox-sensitive nanoagent(DCMn-RA)by growing MnO_(2) on t...Development of tumor microenvironment responsive and multi-mode imaging guided photodynamic therapy(PDT)is highly desired.Herein,we report a MnO_(2)-coated and redox-sensitive nanoagent(DCMn-RA)by growing MnO_(2) on the surface of down-conversion nanoparticles(DCNPs)in situ for integrating GSH detection and enhanced-PDT.In tumor cells,the MnO_(2) layer can be reduced by excess intracellular glutathione(GSH)to Mn^(2+),leading to an intense magnetic resonance(MR)signal as well as recovery of fluorescence of the Ru(II)-polypyridyl alkyne complex(RA)([Ru(bpy)_(2)PIPB]·(PF6)_(2)(bpy=2,2’-bipyridine and PIPB=prop-2-yn^(-1)-yl 4-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)benzoate))for imaging.Meanwhile,the progress of consuming GSH is beneficial for PDT because a high concentration of GSH would eliminate reactive oxygen species(ROS)generated by PDT.In addition,DCMn-RA possesses potential for NIR-II optical imaging upon tissue-penetrable 808 nm excitation.We believe that the research outcomes reveal its promising potential as an integrating theranostic nanoprobe and nanoagent to realize the detection of GSH and enhance the efficacy of PDT.展开更多
Three genetic mechanisms activate oncogenes in human neoplasms: 1) mutations, 2) gene amplification, and 3) chromosome rearrangements. These mechanisms result in either an alteration of protooncogene structure or an i...Three genetic mechanisms activate oncogenes in human neoplasms: 1) mutations, 2) gene amplification, and 3) chromosome rearrangements. These mechanisms result in either an alteration of protooncogene structure or an increase in protooncogene expression. The role of epigenetic aberrancies in carcinogenesis has been described earlier however to clinicians, the biological implications of epigenetic therapies to prevent cancer and the mechanisms involved have been a mystery. Furthermore, there is no biomarker suggested to track the carcinogenesis steps long before cancer develops, and this has caused a significant lack of proactive and preventive measures to be taken as all recommendations in preventive oncology are either deficiently and blindly made or through screening methods which are too late in the game. Here we explored a very different approach by applying our deepest understanding of epigenetics and carcinogenesis and even further we developed a framework where our clinical findings could translate to the research and vice versa by generating advanced and novel hypotheses on “how we get cancer”, by exploring the relation between the host and the tumor cells in a way no one had perceived before. The role of specific cancer stem cell pathways is dissected and how to inhibit each of these initiators using multitargeted epigenetic therapies and off-label medications are explained. We should admit that without considering this sophisticated amazing biological network, cancer will remain an unsolved challenge. Further, we were able to solve this unsolved puzzle by bridging the gap from a hypothetical point of view/hypothesis to possibilities that explain the clinical findings we had observed, and conclude that such an approach can completely change the way practitioners are treating cancer.展开更多
基金supported by the National Nature Science Foundation of China(21877084,21671150,81171646,31170776,and 21472139)the Science and Technology Commission of Shanghai Municipality(14DZ2261100)the Fundamental Research Funds for the Central Universities.
文摘Development of tumor microenvironment responsive and multi-mode imaging guided photodynamic therapy(PDT)is highly desired.Herein,we report a MnO_(2)-coated and redox-sensitive nanoagent(DCMn-RA)by growing MnO_(2) on the surface of down-conversion nanoparticles(DCNPs)in situ for integrating GSH detection and enhanced-PDT.In tumor cells,the MnO_(2) layer can be reduced by excess intracellular glutathione(GSH)to Mn^(2+),leading to an intense magnetic resonance(MR)signal as well as recovery of fluorescence of the Ru(II)-polypyridyl alkyne complex(RA)([Ru(bpy)_(2)PIPB]·(PF6)_(2)(bpy=2,2’-bipyridine and PIPB=prop-2-yn^(-1)-yl 4-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)benzoate))for imaging.Meanwhile,the progress of consuming GSH is beneficial for PDT because a high concentration of GSH would eliminate reactive oxygen species(ROS)generated by PDT.In addition,DCMn-RA possesses potential for NIR-II optical imaging upon tissue-penetrable 808 nm excitation.We believe that the research outcomes reveal its promising potential as an integrating theranostic nanoprobe and nanoagent to realize the detection of GSH and enhance the efficacy of PDT.
文摘Three genetic mechanisms activate oncogenes in human neoplasms: 1) mutations, 2) gene amplification, and 3) chromosome rearrangements. These mechanisms result in either an alteration of protooncogene structure or an increase in protooncogene expression. The role of epigenetic aberrancies in carcinogenesis has been described earlier however to clinicians, the biological implications of epigenetic therapies to prevent cancer and the mechanisms involved have been a mystery. Furthermore, there is no biomarker suggested to track the carcinogenesis steps long before cancer develops, and this has caused a significant lack of proactive and preventive measures to be taken as all recommendations in preventive oncology are either deficiently and blindly made or through screening methods which are too late in the game. Here we explored a very different approach by applying our deepest understanding of epigenetics and carcinogenesis and even further we developed a framework where our clinical findings could translate to the research and vice versa by generating advanced and novel hypotheses on “how we get cancer”, by exploring the relation between the host and the tumor cells in a way no one had perceived before. The role of specific cancer stem cell pathways is dissected and how to inhibit each of these initiators using multitargeted epigenetic therapies and off-label medications are explained. We should admit that without considering this sophisticated amazing biological network, cancer will remain an unsolved challenge. Further, we were able to solve this unsolved puzzle by bridging the gap from a hypothetical point of view/hypothesis to possibilities that explain the clinical findings we had observed, and conclude that such an approach can completely change the way practitioners are treating cancer.
