The spatial arrangement of activating ligands is known to have great influence on T cell activation.However,independently studying each ligand’s spatial organization parameter that affects T cell activation remains a...The spatial arrangement of activating ligands is known to have great influence on T cell activation.However,independently studying each ligand’s spatial organization parameter that affects T cell activation remains a great challenge.Here,with DNA origami,we precisely organized the CD3ɛantibodies simulating T cell receptor(TCR)ligands and CD28 antibodies simulating co-stimulatory ligands to interrogate the independent role of TCR-ligand spacing and local copy numbers as well as the spacing between TCR ligands and co-stimulatory ligands on T cell activation.We found that T cell activation benefited fromlocally concentrated TCR ligands with a shorter spacing and was maximized by an∼38 nm spacing between TCR ligands and co-stimulatory ligands.The T cell expander constructed based on our findings could efficiently expand CD8+T cells for tumor immunotherapy.Thus,the DNA nanostructurebased ligands’precise arrangement can be a unique tool in studying immune cell activations and cellbased immunotherapies.展开更多
Dapsone hypersensitivity syndrome(DHS)was first reported by Lowe and Smith[1]in 1949 in Nigeria and was termed“dapsone syndrome”by Allday and Barnes[2]in 1951.DHS is a drug-induced hypersensitivity syndrome(DIHS)cau...Dapsone hypersensitivity syndrome(DHS)was first reported by Lowe and Smith[1]in 1949 in Nigeria and was termed“dapsone syndrome”by Allday and Barnes[2]in 1951.DHS is a drug-induced hypersensitivity syndrome(DIHS)caused by dapsone 404’-diaminodiphenylsulfone(DDS).DHS is characterized by fever,rash,lymphadenopathy,and hepatitis,which usually develop after patients receive DDS for 5 to 6 weeks.Epidemiological studies have estimated DHS prevalence and fatality rates of 1.4%and 9.9%,respectively.[3]Until recently,the“wait and see”approach was used for patients with suspected DHS.Herein,we review recent developments in DHS research,focusing on its etiology,pathogenesis,diagnosis,and prevention,to make DDS a safer medication for most of the population through the prospective exclusion of susceptible patients before DDS administration.展开更多
It is well known that adaptive immunity involving T cells plays a crucial role in combating many diseases.T-cell activation is initiated by the engagement of T-cell receptors(TCRs)to peptide-loaded major histocompatib...It is well known that adaptive immunity involving T cells plays a crucial role in combating many diseases.T-cell activation is initiated by the engagement of T-cell receptors(TCRs)to peptide-loaded major histocompatibility complexes(p MHCs)on antigen-presenting cells(APCs),which triggers a cascade of signaling events that ultimately lead to T-cell activation[1].展开更多
Ultrasound with deep penetration depth and high security could be adopted in sonodynamic therapy(SDT)by activating sonosensitizers to generate cytotoxic reactive oxygen species(ROS).Herein,two-dimensional(2D)coordinat...Ultrasound with deep penetration depth and high security could be adopted in sonodynamic therapy(SDT)by activating sonosensitizers to generate cytotoxic reactive oxygen species(ROS).Herein,two-dimensional(2D)coordination nanosheets composed of Zn^(2+)and Tetrakis(4-carboxyphenyl)porphyrin(TCPP)are fabricated.While exhibiting greatly enhanced ultrasoundtriggered ROS generation useful for noninvasive SDT,such Zn-TCPP 2D nanosheets show high loading capacity of oligodeoxynudeotides such as cytosine—phosphorothioate-guanine(CpG),which is a potent toll like receptor 9(TLR9)agonist useful in activating immune responses.Highly effective SD T of primary tumors could release tumor-associated antigens,which working together with Zn-TCPP/CpG adjuvant nanosheets could function like whole-tumor-cell vaccines and trigger tumor-specific immune responses.Interestingly,ultrasound itself could strengthen anti-tumor immune responses by improving the tumor-infiltration of T cells and limiting regulatory T cells in the tumor microenvironment.Thus,SDT using Zn-TCPP/CpG nanosheets after destruction of primary tumors could induce potent antitumor immune responses to inhibit distant abscopal tumors without direct SD T treatment.Moreover,SDT with Zn-TCPP/CpG could trigger strong immunological memory effects to inhibit cancer recurrence after elimination of primary tumors.Therefore,the 2D coordination nanosheet may be a promising platform to deliver potent SDT-triggered immunotherapy for highly effective cancer treatment.展开更多
The development of nanomedicine systems for applications in cancer therapies has been widely explored in the last decade.With inherent biocompatibility,nanomedicine devices derived from biological membranes have shown...The development of nanomedicine systems for applications in cancer therapies has been widely explored in the last decade.With inherent biocompatibility,nanomedicine devices derived from biological membranes have shown many unique advantages compared with traditional artificial nanomaterials for biomedical applications.Herein,we present a comprehensive review of the recent development of cell membrane derived nanomedicines in cancer treatment.We firstly outline the advantages of biological membranes in nanomedicine design derived from their intrinsic characteristics,and then discuss the applications of biological membrane derived nanomedicines.For the first major category of membrane-derived nanomedicine,synthetic nanoparticles are usually camouflaged with cell membranes to acquire additional functionalities.The other type of membrane-based nanomedicine is directly using the engineered cell membrane-derived vesicles or nanovesicles secreted by cells for tumor treatment.At last,we discuss the challenges of membrane-derived nanomedicines towards future clinical applications,following with perspectives on possible solutions to the current problems.展开更多
基金supported by the National Research Programs from the Ministry of Science and Technology of China(grant no.2021YFF0701800)the National Natural Science Foundation of China(grant nos.52032008 and 22277071)+1 种基金the Collaborative Innovation Center of Suzhou Nano Science and Technologythe“111”program from the Ministry of Education of China.
文摘The spatial arrangement of activating ligands is known to have great influence on T cell activation.However,independently studying each ligand’s spatial organization parameter that affects T cell activation remains a great challenge.Here,with DNA origami,we precisely organized the CD3ɛantibodies simulating T cell receptor(TCR)ligands and CD28 antibodies simulating co-stimulatory ligands to interrogate the independent role of TCR-ligand spacing and local copy numbers as well as the spacing between TCR ligands and co-stimulatory ligands on T cell activation.We found that T cell activation benefited fromlocally concentrated TCR ligands with a shorter spacing and was maximized by an∼38 nm spacing between TCR ligands and co-stimulatory ligands.The T cell expander constructed based on our findings could efficiently expand CD8+T cells for tumor immunotherapy.Thus,the DNA nanostructurebased ligands’precise arrangement can be a unique tool in studying immune cell activations and cellbased immunotherapies.
基金Academic promotion program of Shandong First Medical University(Nos.2019LJ002,2019RC007,2020RC001)Youth technology Innovation Support Project of Shandong Colleges and Universities(No.2019KJL003)+2 种基金National Natural Science Foundation of China(Nos.81811530342,81972946,81903224,82103734)Shandong Provincial Foreign Expert Project(No.WST2019004)China Scholarship Council(No.201806220227)
文摘Dapsone hypersensitivity syndrome(DHS)was first reported by Lowe and Smith[1]in 1949 in Nigeria and was termed“dapsone syndrome”by Allday and Barnes[2]in 1951.DHS is a drug-induced hypersensitivity syndrome(DIHS)caused by dapsone 404’-diaminodiphenylsulfone(DDS).DHS is characterized by fever,rash,lymphadenopathy,and hepatitis,which usually develop after patients receive DDS for 5 to 6 weeks.Epidemiological studies have estimated DHS prevalence and fatality rates of 1.4%and 9.9%,respectively.[3]Until recently,the“wait and see”approach was used for patients with suspected DHS.Herein,we review recent developments in DHS research,focusing on its etiology,pathogenesis,diagnosis,and prevention,to make DDS a safer medication for most of the population through the prospective exclusion of susceptible patients before DDS administration.
文摘It is well known that adaptive immunity involving T cells plays a crucial role in combating many diseases.T-cell activation is initiated by the engagement of T-cell receptors(TCRs)to peptide-loaded major histocompatibility complexes(p MHCs)on antigen-presenting cells(APCs),which triggers a cascade of signaling events that ultimately lead to T-cell activation[1].
基金the National Research Programs of China(No.2016YFA0201200)the National Natural Science Foundation of China(Nos.91959104,21927803,51903182,51525203,)+1 种基金the Natural Science Foundation of Jiangsu Province(No.BK20190826)Collaborative Innovation Center of Suzhou Nano Science and Technology,and the 111 Program from the Ministry of Education of China.
文摘Ultrasound with deep penetration depth and high security could be adopted in sonodynamic therapy(SDT)by activating sonosensitizers to generate cytotoxic reactive oxygen species(ROS).Herein,two-dimensional(2D)coordination nanosheets composed of Zn^(2+)and Tetrakis(4-carboxyphenyl)porphyrin(TCPP)are fabricated.While exhibiting greatly enhanced ultrasoundtriggered ROS generation useful for noninvasive SDT,such Zn-TCPP 2D nanosheets show high loading capacity of oligodeoxynudeotides such as cytosine—phosphorothioate-guanine(CpG),which is a potent toll like receptor 9(TLR9)agonist useful in activating immune responses.Highly effective SD T of primary tumors could release tumor-associated antigens,which working together with Zn-TCPP/CpG adjuvant nanosheets could function like whole-tumor-cell vaccines and trigger tumor-specific immune responses.Interestingly,ultrasound itself could strengthen anti-tumor immune responses by improving the tumor-infiltration of T cells and limiting regulatory T cells in the tumor microenvironment.Thus,SDT using Zn-TCPP/CpG nanosheets after destruction of primary tumors could induce potent antitumor immune responses to inhibit distant abscopal tumors without direct SD T treatment.Moreover,SDT with Zn-TCPP/CpG could trigger strong immunological memory effects to inhibit cancer recurrence after elimination of primary tumors.Therefore,the 2D coordination nanosheet may be a promising platform to deliver potent SDT-triggered immunotherapy for highly effective cancer treatment.
基金This work was partially supported by the National Research Programs from Ministry of Science and Technology of China(2016YFA0201200)the National Natural Science Foundation of China(21907073,52032008)+1 种基金the Jiangsu Social Development Project(BE2019658)Collaborative Innovation Center of Suzhou Nano Science and Technology,the “111” program from the Ministry of Education of China and the Key Scientific and Technological Projects of Henan Province of China(192102310071).
文摘The development of nanomedicine systems for applications in cancer therapies has been widely explored in the last decade.With inherent biocompatibility,nanomedicine devices derived from biological membranes have shown many unique advantages compared with traditional artificial nanomaterials for biomedical applications.Herein,we present a comprehensive review of the recent development of cell membrane derived nanomedicines in cancer treatment.We firstly outline the advantages of biological membranes in nanomedicine design derived from their intrinsic characteristics,and then discuss the applications of biological membrane derived nanomedicines.For the first major category of membrane-derived nanomedicine,synthetic nanoparticles are usually camouflaged with cell membranes to acquire additional functionalities.The other type of membrane-based nanomedicine is directly using the engineered cell membrane-derived vesicles or nanovesicles secreted by cells for tumor treatment.At last,we discuss the challenges of membrane-derived nanomedicines towards future clinical applications,following with perspectives on possible solutions to the current problems.