Cancer vaccines represent a promising immunotherapeutic treatment modality.The promotion of cross-presentation of extracellular tumor-associated antigens on the major histocompatibility complex(MHC) class I molecules ...Cancer vaccines represent a promising immunotherapeutic treatment modality.The promotion of cross-presentation of extracellular tumor-associated antigens on the major histocompatibility complex(MHC) class I molecules and dendritic cell maturation at the appropriate time and place is crucial for cancer vaccines to prime cytolytic T cell response with reduced side effects.Current vaccination strategies,however,are not able to achieve the spatiotemporal control of antigen cross-presentation.Here,we report a liposomal vaccine loading the second near-infrared window(NIR-II,1000—1700 nm) fluorophore BPBBT with an efficient photothermal conversion effect that offers an NIR-light-triggered endolysosomal escape under the imaging guidance.The NIR-II image-guided vaccination strategy specifically controls the cytosolic delivery of antigens for cross-presentation in the draining lymph nodes(DLNs).Moreover,the photothermally induced endolysosomal rupture initiates autophagy.We also find that the adjuvant simvastatin acts as an autophagy activator through inhibiting the PI3K/AKT/m TOR pathway.The light-induced autophagy in the DLNs together with simvastatin treatment cooperatively increase MHC class II expression by activating autophagy machinery for dendritic cell maturation.This study presents a paradigm of NIR-II image-guided light-triggered vaccination.The approach for remote control of antigen cross-presentation and autophagy represents a new strategy for vaccine development.展开更多
The exploration of novel photo/thermal-responsive nonvolatile memorizers will be beneficial for energysaving memories.Herein,new<110>-oriented perovskites using single template melamine,i.e.,[(MLAI-H_(2))(PbX_(4...The exploration of novel photo/thermal-responsive nonvolatile memorizers will be beneficial for energysaving memories.Herein,new<110>-oriented perovskites using single template melamine,i.e.,[(MLAI-H_(2))(PbX_(4))]_n(X=Br (α-1),Cl (α-2),MLAI=melamine) have been prepared and their structures upon irradiation of visible light have been investigated.They have been fabricated as nonvolatile memory devices with structures of ITO/[(MLAI-H_(2))(PbX_(4))]_n/PMMA/Ag (device-1:X=Br,device-2:X=Cl),which can exhibit unique visible light-triggered binary nonvolatile memory performances.Interestingly,the silent or working status can be monitored by visible chromisms.Furthermore,the light-triggered binary resistive switching mechanisms of these ITO/[(MLAI-H_(2))(PbX_(4))]_n/PMMA/Ag memory devices have been clarified in terms of EPR,fluorescence,and single-crystal structural analysis.The presence of light-activated traps in<110>-oriented[(MLAI-H_(2))(PbX_(4))]_n perovskites are dominated in the appearance of light-triggered resistive switching behaviors,based on which the inverted internal electrical fields can be established.According to the structural analysis,the more distorted PbX_6octahedra,higher corrugated<110>-oriented perovskite sheets,and more condensed organic-inorganic packing in Br-containing perovskite are beneficial for the stabilization of light-activated traps,which lead to the better resistive switching behavior of device-1.This work can pave a new avenue for the establishment of novel energy-saving nonvolatile memorizers used in aerospace or military industries.展开更多
Immunotherapy emerged as a paradigm shift in cancer treatments, which can effectively inhibit cancer progression by activating the immune system. Remarkable clinical outcomes have been achieved through recent advances...Immunotherapy emerged as a paradigm shift in cancer treatments, which can effectively inhibit cancer progression by activating the immune system. Remarkable clinical outcomes have been achieved through recent advances in cancer immunotherapy, including checkpoint blockades, adoptive cellular therapy, cancer vaccine, and tumor microenvironment modulation. However, extending the application of immunotherapy in cancer patients has been limited by the low response rate and side effects such as autoimmune toxicities. With great progress being made in nanotechnology, nanomedicine has been exploited to overcome biological barriers for drug delivery. Given the spatiotemporal control,light-responsive nanomedicine is of great interest in designing precise modality for cancer immunotherapy. Herein, we summarized current research utilizing light-responsive nanoplatforms to enhance checkpoint blockade immunotherapy, facilitate targeted delivery of cancer vaccines, activate immune cell functions, and modulate tumor microenvironment. The clinical translation potential of those designs is highlighted and challenges for the next breakthrough in cancer immunotherapy are discussed.展开更多
Treatment of implant-associated infection is becoming more challenging,especially when bacterial biofilms form on the surface of the implants.Developing multi-mechanism antibacterial methods to combat bacterial biofil...Treatment of implant-associated infection is becoming more challenging,especially when bacterial biofilms form on the surface of the implants.Developing multi-mechanism antibacterial methods to combat bacterial biofilm infections by the synergistic effects are superior to those based on single modality due to avoiding the adverse effects arising from the latter.In this work,TiO2 nanorod arrays in combination with irradiation with 808 nearinfrared(NIR)light are proven to eradicate single specie biofilms by combining photothermal therapy,photodynamic therapy,and physical killing of bacteria.The TiO2 nanorod arrays possess efficient photothermal conversion ability and produce a small amount of reactive oxygen species(ROS).Physiologically,the combined actions of hyperthermia,ROS,and puncturing by nanorods give rise to excellent antibacterial properties on titanium requiring irradiation for only 15 min as demonstrated by our experiments conducted in vitro and in vivo.More importantly,bone biofilm infection is successfully treated efficiently by the synergistic antibacterial effects and at the same time,the TiO2 nanorod arrays improve the new bone formation around implants.In this protocol,besides the biocompatible TiO2 nanorod arrays,an extra photosensitizer is not needed and no other ions would be released.Our findings reveal a rapid bacteria-killing method based on the multiple synergetic antibacterial modalities with high biosafety that can be implemented in vivo and obviate the need for a second operation.The concept and antibacterial system described here have large clinical potential in orthopedic and dental applications.展开更多
基金supported in part by grants from National Natural Science Foundation of China(No.81991493,China)Shanghai Municipal Health Commission(No.2022XD045,China)。
文摘Cancer vaccines represent a promising immunotherapeutic treatment modality.The promotion of cross-presentation of extracellular tumor-associated antigens on the major histocompatibility complex(MHC) class I molecules and dendritic cell maturation at the appropriate time and place is crucial for cancer vaccines to prime cytolytic T cell response with reduced side effects.Current vaccination strategies,however,are not able to achieve the spatiotemporal control of antigen cross-presentation.Here,we report a liposomal vaccine loading the second near-infrared window(NIR-II,1000—1700 nm) fluorophore BPBBT with an efficient photothermal conversion effect that offers an NIR-light-triggered endolysosomal escape under the imaging guidance.The NIR-II image-guided vaccination strategy specifically controls the cytosolic delivery of antigens for cross-presentation in the draining lymph nodes(DLNs).Moreover,the photothermally induced endolysosomal rupture initiates autophagy.We also find that the adjuvant simvastatin acts as an autophagy activator through inhibiting the PI3K/AKT/m TOR pathway.The light-induced autophagy in the DLNs together with simvastatin treatment cooperatively increase MHC class II expression by activating autophagy machinery for dendritic cell maturation.This study presents a paradigm of NIR-II image-guided light-triggered vaccination.The approach for remote control of antigen cross-presentation and autophagy represents a new strategy for vaccine development.
基金financially supported by the Natural Science Foundation of Fujian Province(Nos.2021J02007,2021J01553)Fujian Science&Technology Innovation Laboratory for Optoelectronic Information of China(No.2021ZR148)。
文摘The exploration of novel photo/thermal-responsive nonvolatile memorizers will be beneficial for energysaving memories.Herein,new<110>-oriented perovskites using single template melamine,i.e.,[(MLAI-H_(2))(PbX_(4))]_n(X=Br (α-1),Cl (α-2),MLAI=melamine) have been prepared and their structures upon irradiation of visible light have been investigated.They have been fabricated as nonvolatile memory devices with structures of ITO/[(MLAI-H_(2))(PbX_(4))]_n/PMMA/Ag (device-1:X=Br,device-2:X=Cl),which can exhibit unique visible light-triggered binary nonvolatile memory performances.Interestingly,the silent or working status can be monitored by visible chromisms.Furthermore,the light-triggered binary resistive switching mechanisms of these ITO/[(MLAI-H_(2))(PbX_(4))]_n/PMMA/Ag memory devices have been clarified in terms of EPR,fluorescence,and single-crystal structural analysis.The presence of light-activated traps in<110>-oriented[(MLAI-H_(2))(PbX_(4))]_n perovskites are dominated in the appearance of light-triggered resistive switching behaviors,based on which the inverted internal electrical fields can be established.According to the structural analysis,the more distorted PbX_6octahedra,higher corrugated<110>-oriented perovskite sheets,and more condensed organic-inorganic packing in Br-containing perovskite are beneficial for the stabilization of light-activated traps,which lead to the better resistive switching behavior of device-1.This work can pave a new avenue for the establishment of novel energy-saving nonvolatile memorizers used in aerospace or military industries.
基金supported by Hong Kong Research Grants Council, University Grants Committee (No. 2711522, Hong Kong, China)Ming Wai Lau Centre for Reparative Medicine (Associate Member Programme, Hong Kong, China)。
文摘Immunotherapy emerged as a paradigm shift in cancer treatments, which can effectively inhibit cancer progression by activating the immune system. Remarkable clinical outcomes have been achieved through recent advances in cancer immunotherapy, including checkpoint blockades, adoptive cellular therapy, cancer vaccine, and tumor microenvironment modulation. However, extending the application of immunotherapy in cancer patients has been limited by the low response rate and side effects such as autoimmune toxicities. With great progress being made in nanotechnology, nanomedicine has been exploited to overcome biological barriers for drug delivery. Given the spatiotemporal control,light-responsive nanomedicine is of great interest in designing precise modality for cancer immunotherapy. Herein, we summarized current research utilizing light-responsive nanoplatforms to enhance checkpoint blockade immunotherapy, facilitate targeted delivery of cancer vaccines, activate immune cell functions, and modulate tumor microenvironment. The clinical translation potential of those designs is highlighted and challenges for the next breakthrough in cancer immunotherapy are discussed.
基金supported by the National Natural Science Foundation of China (51902098, 51972105, 51525202, and 61574054)the Hunan Provincial Natural Science Foundation (2018RS3051).
基金the National Natural Science Foundation of China(31700834 and 11632013)Major Projects in Research and Development of Shanxi(Projects of International Cooperation,201803D421090)+2 种基金Fund for Shanxi“1331 Project”Key Innovative Research Team(PY201809)Hong Kong Research Grants Council(RGC)General Research Funds(GRF)(CityU 11205617)Guangdong-Hong Kong Technology Cooperation Funding Scheme(TCFS)GHP/085/18SZ(CityU 9440230).
文摘Treatment of implant-associated infection is becoming more challenging,especially when bacterial biofilms form on the surface of the implants.Developing multi-mechanism antibacterial methods to combat bacterial biofilm infections by the synergistic effects are superior to those based on single modality due to avoiding the adverse effects arising from the latter.In this work,TiO2 nanorod arrays in combination with irradiation with 808 nearinfrared(NIR)light are proven to eradicate single specie biofilms by combining photothermal therapy,photodynamic therapy,and physical killing of bacteria.The TiO2 nanorod arrays possess efficient photothermal conversion ability and produce a small amount of reactive oxygen species(ROS).Physiologically,the combined actions of hyperthermia,ROS,and puncturing by nanorods give rise to excellent antibacterial properties on titanium requiring irradiation for only 15 min as demonstrated by our experiments conducted in vitro and in vivo.More importantly,bone biofilm infection is successfully treated efficiently by the synergistic antibacterial effects and at the same time,the TiO2 nanorod arrays improve the new bone formation around implants.In this protocol,besides the biocompatible TiO2 nanorod arrays,an extra photosensitizer is not needed and no other ions would be released.Our findings reveal a rapid bacteria-killing method based on the multiple synergetic antibacterial modalities with high biosafety that can be implemented in vivo and obviate the need for a second operation.The concept and antibacterial system described here have large clinical potential in orthopedic and dental applications.
