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
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.
