Zwitterionic polymer materials have been extensively studied,but zwitterionic peptides supramolecular hydrogel materials are rarely studied.In this study,the preparation of two zwitterionic hydrogels using self-assemb...Zwitterionic polymer materials have been extensively studied,but zwitterionic peptides supramolecular hydrogel materials are rarely studied.In this study,the preparation of two zwitterionic hydrogels using self-assembled peptides were reported.The hydrogels could be fabricated easily by changing the temperature or enzyme catalysis in a short time.And the differences in structure and function of the zwitterion peptide hydrogels caused by the two preparation methods were also be compared.We found that the hydrogel prepared by enzyme induced self-assembly has better solubility and lower cytotoxicity than that prepared by the heating-cooling process.The result showed the enzyme induced self-assembly way to form zwitterionic peptides supramolecular hydrogel materials could have further biomedical applications.展开更多
The selective identification and removal of senescent cells including senescent cancer cells are very important to prolong life and improve the treatment efficacy of cancer therapy.In this study,we integrated the high...The selective identification and removal of senescent cells including senescent cancer cells are very important to prolong life and improve the treatment efficacy of cancer therapy.In this study,we integrated the high selectivity of enzyme-instructed selfassembly(EISA)and efficient reactive oxygen species(ROS)generating property of a novel luminogen with aggregationinduced emission(AIE)character to selectively identify and remove senescent He La(s-He La)cells.The s-He La cells expressed high levels ofβ-galactosidase(β-Gal),which led to the selective accumulation and formation of nanomaterials of Comp.1 in the cells.Upon white light irradiation,the nanomaterials efficiently produced ROS and therefore killed s-He La cells.Our study demonstrated a promising strategy to selectively remove senescent cells and improve the treatment efficacy of cancer therapy.展开更多
The selective formation of nanomaterials in cancer cells and tumors holds great promise for cancer diagnostics and therapy.Until now,most strategies rely on a single trigger to control the formation of nanomaterials i...The selective formation of nanomaterials in cancer cells and tumors holds great promise for cancer diagnostics and therapy.Until now,most strategies rely on a single trigger to control the formation of nanomaterials in situ.The combination of two or more triggers may provide for more sophisticated means of manipulation.In this study,we rationally designed a molecule(Comp.1)capable of responding to two enzymes,alkaline phosphatase(ALP),and reductase.Since the A549 lung cancer cell line showed elevated levels of extracellular ALP and intracellular reductase,we demonstrated that Comp.1 responded in a stepwise fashion to those two enzymes and displayed a tandem molecular self-assembly behavior.The selective formation of nanofibers in the mitochondria of the lung cancer cells led to the disruption of the mitochondrial membrane,resulting in an increased level of reactive oxygen species(ROS)and the release of cytochrome C(Cyt C).ROS can react with proteins,resulting in endoplasmic reticulum(ER)stress and the unfolded protein response(UPR).This severe ER stress led to disruption of the ER,formation of vacuoles,and ultimately,apoptosis of the A549 cells.Therefore,Comp.1 could selectively inhibit lung cancer cells in vitro and A549 xenograft tumors in vivo.Our study provides a novel strategy for the selective formation of nanomaterials in lung cancer cells,which is powerful and promising for the diagnosis and treatment of lung cancer.展开更多
Immunogenic cell death(ICD) plays a major role in cancer immunotherapy by stimulating specific T cell responses and restoring the antitumor immune system.However,effective type Ⅱ ICD inducers without biotoxicity are ...Immunogenic cell death(ICD) plays a major role in cancer immunotherapy by stimulating specific T cell responses and restoring the antitumor immune system.However,effective type Ⅱ ICD inducers without biotoxicity are still very limited.Herein,a tentative drug-or photo sensitizer-free strategy was developed by employing enzymatic self-assembly of the peptide F-pY-T to induce mitochondrial oxidative stress in cancer cells.Upon dephosphorylation catalyzed by alkaline phosphatase overexpressed on cancer cells,the peptide F-pY-T self-assembled to form nanoparticles,which were subsequently internalized.These affected the morphology of mitochondria and induced serious reactive oxygen species production,causing the ICD characterized by the release of danger-associated molecular patterns(DAMPs).DAMPs enhanced specific immune responses by promoting the maturation of DCs and the intratumoral infiltration of tumor-specific T cells to eradicate tumor cells.The dramatic immunotherapeutic capacity could be enhanced further by combination therapy of F-pY-T and anti-PD-L1 agents without visible biotoxicity in the main organs.Thus,our results revealed an alternative strategy to induce efficient ICD by physically promoting mitochondrial oxidative stress.展开更多
基金supported by National Natural Science Foundation of China(Nos.51773097 and 51973096)the Young Elite Scientists Sponsorship Program by Tianjin(No.TJSQNTJ-2017-16)the Fundamental Research Funds for the Central Universities.
文摘Zwitterionic polymer materials have been extensively studied,but zwitterionic peptides supramolecular hydrogel materials are rarely studied.In this study,the preparation of two zwitterionic hydrogels using self-assembled peptides were reported.The hydrogels could be fabricated easily by changing the temperature or enzyme catalysis in a short time.And the differences in structure and function of the zwitterion peptide hydrogels caused by the two preparation methods were also be compared.We found that the hydrogel prepared by enzyme induced self-assembly has better solubility and lower cytotoxicity than that prepared by the heating-cooling process.The result showed the enzyme induced self-assembly way to form zwitterionic peptides supramolecular hydrogel materials could have further biomedical applications.
基金supported by the National Key Research and Development Program of China(2017YFC2103502,2017YFE0132200)the Fundamental Research Funds for the Central Universities,the National Natural Science Fundation of China(31870949,31670973)Tianjin Science Fund for Distinguished Young Scholars(17JCJQJC44900).
文摘The selective identification and removal of senescent cells including senescent cancer cells are very important to prolong life and improve the treatment efficacy of cancer therapy.In this study,we integrated the high selectivity of enzyme-instructed selfassembly(EISA)and efficient reactive oxygen species(ROS)generating property of a novel luminogen with aggregationinduced emission(AIE)character to selectively identify and remove senescent He La(s-He La)cells.The s-He La cells expressed high levels ofβ-galactosidase(β-Gal),which led to the selective accumulation and formation of nanomaterials of Comp.1 in the cells.Upon white light irradiation,the nanomaterials efficiently produced ROS and therefore killed s-He La cells.Our study demonstrated a promising strategy to selectively remove senescent cells and improve the treatment efficacy of cancer therapy.
基金This work is supported by the National Science Fund for Distinguished Young Scholars(31825012)the National Key Research and Development Program of China(2017YFC1103502)+1 种基金the Fundamental Research Funds for the Central Universities,NSFC(31870949 and 51673150)the Tianjin Science Fund for Distinguished Young Scholars(17JCJQJC44900).
文摘The selective formation of nanomaterials in cancer cells and tumors holds great promise for cancer diagnostics and therapy.Until now,most strategies rely on a single trigger to control the formation of nanomaterials in situ.The combination of two or more triggers may provide for more sophisticated means of manipulation.In this study,we rationally designed a molecule(Comp.1)capable of responding to two enzymes,alkaline phosphatase(ALP),and reductase.Since the A549 lung cancer cell line showed elevated levels of extracellular ALP and intracellular reductase,we demonstrated that Comp.1 responded in a stepwise fashion to those two enzymes and displayed a tandem molecular self-assembly behavior.The selective formation of nanofibers in the mitochondria of the lung cancer cells led to the disruption of the mitochondrial membrane,resulting in an increased level of reactive oxygen species(ROS)and the release of cytochrome C(Cyt C).ROS can react with proteins,resulting in endoplasmic reticulum(ER)stress and the unfolded protein response(UPR).This severe ER stress led to disruption of the ER,formation of vacuoles,and ultimately,apoptosis of the A549 cells.Therefore,Comp.1 could selectively inhibit lung cancer cells in vitro and A549 xenograft tumors in vivo.Our study provides a novel strategy for the selective formation of nanomaterials in lung cancer cells,which is powerful and promising for the diagnosis and treatment of lung cancer.
基金supported by the National Natural Science Foundation of China (31870949,21875116,31961143004,81921004,81100942,81472081)the National Science Fund for Distinguished Young Scholars (31825012,China)the Tianjin Science Fund for Distinguished Young Scholars (17JCJQJC44900,China)。
文摘Immunogenic cell death(ICD) plays a major role in cancer immunotherapy by stimulating specific T cell responses and restoring the antitumor immune system.However,effective type Ⅱ ICD inducers without biotoxicity are still very limited.Herein,a tentative drug-or photo sensitizer-free strategy was developed by employing enzymatic self-assembly of the peptide F-pY-T to induce mitochondrial oxidative stress in cancer cells.Upon dephosphorylation catalyzed by alkaline phosphatase overexpressed on cancer cells,the peptide F-pY-T self-assembled to form nanoparticles,which were subsequently internalized.These affected the morphology of mitochondria and induced serious reactive oxygen species production,causing the ICD characterized by the release of danger-associated molecular patterns(DAMPs).DAMPs enhanced specific immune responses by promoting the maturation of DCs and the intratumoral infiltration of tumor-specific T cells to eradicate tumor cells.The dramatic immunotherapeutic capacity could be enhanced further by combination therapy of F-pY-T and anti-PD-L1 agents without visible biotoxicity in the main organs.Thus,our results revealed an alternative strategy to induce efficient ICD by physically promoting mitochondrial oxidative stress.
