Abstract：
:CD47, a "don't eat me" signal, is over-expressed on the surface of most tumors that interacts with signal regulatory protein α (SIRPα) on phagocytic cells. By engaging SIRPα, CD47 limits the ability of macrophages to engulf tumor cells, which acts as a major phagocytic barrier. In this study, we developed an exosome-based immune checkpoint blockade that antagonizes the interaction between CD47 and SIRPα. These exosomes harboring SIRPα variants (SIRPα-exosomes) were sufficient to induce remarkably augmented tumor phagocytosis, lead to prime effective anti-tumor T cell response. Given that clustering of native CD47 provides a high binding avidity to ligate dimerized SIRPα on macrophage, nature-derived exosomes could be appreciable platform to antagonize CD47. Disruption of CD47-SIRPα interaction by SIRPα-exosomes leads to an increase in cells being engulfed by macrophages and a concomitant inhibition of tumor growth in tumor-bearing mice. Moreover, SIRPα-exosomes therapy promotes an intensive T cell infiltration in syngeneic mouse models of cancer, raising the possibility of CD47-targeted therapies to unleash both an innate and adaptive anti-tumor response. Note that very small amount of exosomal SIRPα proteins could effectively lead to phagocytic elimination of tumor cells both in vitro and in vivo. Our results suggest that superlative exosome-based platform has broad potential to maximize the therapeutic efficacy of membrane-associated protein therapeutics.
journal_name
Biomaterialsjournal_title
Biomaterialsauthors
Koh E,Lee EJ,Nam GH,Hong Y,Cho E,Yang Y,Kim ISdoi
10.1016/j.biomaterials.2017.01.004subject
Has Abstractpub_date
2017-03-01 00:00:00pages
121-129eissn
0142-9612issn
1878-5905pii
S0142-9612(17)30004-2journal_volume
121pub_type
杂志文章相关文献
BIOMATERIALS文献大全abstract：:Intracellular-acting therapeutic proteins offer a promising clinical alternative to extracellular-acting agents, but are limited in efficacy by their low permeability into the cell cytoplasm. We have developed a nanoparticle (NP) composed of lipid (DOTAP/DOPE) and apolipoprotein (APOA-I) to mediate the targeted delive...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/j.biomaterials.2012.02.010
更新日期：2012-05-01 00:00:00
abstract：:The purpose of this study was to determine the mechanical properties and the atomistic structures of various gelatin hydrogels as a preliminary to using these in bioengineering applications. The hydrogels were investigated as neat materials and as particulate-reinforced composites both in the as-formed state and follo...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/s0142-9612(02)00274-0
更新日期：2003-01-01 00:00:00
abstract：:The microstructure of TiTa30 alloys diffusion bonded to a 99.7 wt% Al2O3 ceramic was subdivided into a reaction double layer containing the intermetallic phases TiAl and Ti3Al and the (alpha + beta) Ti microstructure. Excellent fracture toughness data of the TiTa30/Al2O3 joints of about 37 J/m2 were obtained after wel...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/0142-9612(92)90166-l
更新日期：1992-01-01 00:00:00
abstract：:Intestinal organoids are widely applied in stem cell research, regenerative medicine, toxicology, pharmacology, and host-microbe interactions research. The variability of oxidative metabolism for stem and differentiated cell types constituting organoid is known to be important but so far it has not been studied in det...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/j.biomaterials.2017.08.043
更新日期：2017-11-01 00:00:00
abstract：:Drug hepatotoxicity testing requires in vitro hepatocyte culture to maintain the long-term and stable liver specific functions. We developed a drug testing platform based on laminar-flow immediate-overlay hepatocyte sandwich perfusion culture. The immediate-overlay sandwich (collagen-coated porous polymeric membrane a...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/j.biomaterials.2009.07.022
更新日期：2009-10-01 00:00:00
abstract：:Autophagy has attracted a great deal of research interest in tumor therapy in recent years. An attempt was made in this direction and now we report that iron oxide NPs synthesized by us selectively induce autophagy in cancer cells (A549) and not in normal cells (IMR-90). It was also noteworthy that autophagy correlate...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/j.biomaterials.2011.10.080
更新日期：2012-02-01 00:00:00
abstract：:The degree of metal ion dissolution from Ti-6Al-4V alloy hip replacement stems subjected to various mechanical and chemical surface pretreatments was analysed in vitro. High-dissolution rates were observed for nitric acid passivated samples that had been mechanically surface treated to increase the implant surface are...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/s0142-9612(99)00200-8
更新日期：2000-02-01 00:00:00
abstract：:Doxorubicin (DOX) is a well-known anticancer drug used for the treatment of a wide variety of cancers. However, undesired toxicity of DOX limits its uses. To address the issue of minimizing toxicity of DOX by making it targeted towards cancer cells, DOX was entrapped in self-assembled 6-O-(3-hexadecyloxy-2-hydroxyprop...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/j.biomaterials.2012.12.044
更新日期：2013-04-01 00:00:00
abstract：:Increasing knowledge about molecular mechanisms of endogenous RNA interference (RNAi) and small interfering RNAs (siRNAs) has been incorporated into innovative nucleic acid medicines for treatment of diseases such as cancers. Although RNAi and siRNA have the potential to become powerful therapeutic drugs, their delive...
journal_title：Biomaterials
pub_type： 杂志文章,评审
doi：10.1016/j.biomaterials.2012.06.068
更新日期：2012-10-01 00:00:00
abstract：:Right femoral, cortical bone osteotomies of 42 rabbits were fixed with fibrillated, self-reinforced (SR) poly-L-lactide (PLLA) rods, 4.5 mm in diameter. Follow-up times were from 3 to 48 wk. None of the rods broke during this period. There was one non-union at three weeks and one non-union at 12 weeks. Radiographic, h...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/0142-9612(93)90123-j
更新日期：1993-01-01 00:00:00
abstract：:A nanohybrid vesicle was developed from cholesteryl succinyl silane(CSS) in combination of sol-gel process and self-assembly technique. The silicalike surface adds CSS vesicles remarkably high stability against destabilization in blood or leakage of drug cargos. It was found that CSS vesicles alone exhibited selective...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/j.biomaterials.2011.08.043
更新日期：2011-12-01 00:00:00
abstract：:Tetragonal zirconia polycrystal (TZP) is a new interesting ceramic for the manufacture of medical devices. Its wide use in orthopedic and odontoiatric implants was limited till now by the high chemical and radiochemical impurities of the raw materials. Purification processes now available allow to obtain high purity c...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/s0142-9612(98)00182-3
更新日期：1999-02-01 00:00:00
abstract：:In the present work, we designed and synthesized a novel mono-guanidine heterolipid (MGH) and confirmed its structure by NMR and ESI-MS. The MGH was used as cationic lipid in developing etoposide loaded cationic self-microemulsifying drug delivery system (ECS) intended to be delivered by intratumoral route. The ECS ex...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/j.biomaterials.2015.03.040
更新日期：2015-07-01 00:00:00
abstract：:Primary canine oral mucosal epithelial cells were cultured on temperature-responsive dishes and cell culture inserts to fabricate transplantable epithelial cell sheets. When 3T3 feeder layers and fetal bovine serum were eliminated from dish culture, the harvested cell sheets became significantly more fragile. In contr...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/j.biomaterials.2006.05.042
更新日期：2006-11-01 00:00:00
abstract：:The development of an efficient colorectal cancer therapy is currently a public health priority. In the present work, we proposed a multifunctional theranostic micellar drug delivery system utilizing cationic PDMA-block-poly(ε-caprolactone) (PDMA-b-PCL) micelles as nanocarriers of SN-38 (7-ethyl-10-hydroxycamptothecin...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/j.biomaterials.2016.01.068
更新日期：2016-04-01 00:00:00
abstract：:The porous TiO2/perlite composite Ecopore is a synthetic biomaterial with possible clinical application in bone substitution. In our previous work, we demonstrated that surface modification of Ecopore with fibronectin (FN) enhanced spreading and growth of human osteoblasts in vitro. In the present study, we implanted ...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/j.biomaterials.2005.08.001
更新日期：2006-03-01 00:00:00
abstract：:The design of bioartificial liver assist device requires an effective attachment of primary hepatocytes on polymeric biomaterials. A better understanding of this cell-surface interaction would aid the optimal choice of biomaterials. In this study, the adhesion contact dynamics of primary hepatocytes on poly(ethylene t...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/j.biomaterials.2004.03.041
更新日期：2005-03-01 00:00:00
abstract：:A variety of approaches have been investigated to address the problems associated with oral insulin delivery, but the bioavailability of oral insulin is still low. Insulin is rapidly degraded by the enzymes in the GI tract and is not transported across the epithelial barrier easily. The oral insulin formulation develo...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/j.biomaterials.2006.02.026
更新日期：2006-07-01 00:00:00
abstract：:The long-term behaviour of cellulose sponge implants, 10 x 10 x 5 mm in size, and tissue reactions in and around them were examined in the subcutaneous tissue of the rat from 1 to 60 weeks after implantation. The cellulose sponge used was filled up with connective tissue 4 to 8 weeks after implantation. Histologically...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/s0142-9612(99)00094-0
更新日期：1999-11-01 00:00:00
abstract：:The ability to precisely pattern embryonic stem (ES) cells in vitro into predefined arrays/geometries may allow for the recreation of a stem cell niche for better understanding of how cellular microenvironmental factors govern stem cell maintenance and differentiation. In this study, a new gelatin-based laser direct-w...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/j.biomaterials.2010.11.015
更新日期：2011-03-01 00:00:00
abstract：:Crystalline carbonate- and sodium-and-carbonate-substituted hydroxyapatite (CO3HAp and NaCO3HAp) powders were prepared at room temperature via a heterogeneous reaction between Ca(OH)2/CaCO3/Na2CO3 and (NH4)2HPO4 aqueous solution using the mechanochemical hydrothermal route. X-ray diffraction, infrared spectroscopy, th...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/s0142-9612(01)00158-2
更新日期：2002-02-01 00:00:00
abstract：:Most urgent health problems are related to a blood vessel formation failure. The use of stem cells from different sources or species for both in vitro and in vivo engineering of endothelium does not necessarily imply their direct commitment towards a vascular phenotype. In the present study, we used human amniotic flu...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/j.biomaterials.2011.01.071
更新日期：2011-05-01 00:00:00
abstract：:Dacron velour is often used to anchor a percutaneous device, like the catheter used in peritoneal dialysis. However, exit-site infections complicate this method of dialysis and are supposed to be related to the design of the catheter. In animal experiments, a percutaneous device provided with a titanium fibre mesh to ...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/0142-9612(96)84946-5
更新日期：1996-06-01 00:00:00
abstract：:We developed a strategy to formulate supraparamagnetic iron oxides (SPIOs) in nanoparticles (NPs) of biodegradable copolymer made up of poly(lactic acid) (PLA) and d-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS) for medical imaging by magnetic resonance imaging (MRI) of high contrast and low side effects....
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/j.biomaterials.2010.03.070
更新日期：2010-07-01 00:00:00
abstract：:The aim of this study was to identify and quantify potential regional and directional variations in the quasistatic uniaxial mechanical properties of the passive urinary bladder wall. Overall, the lower body and trigone regions demonstrated the highest degree of directional anisotropy, whereas the ventral region demon...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/j.biomaterials.2008.09.034
更新日期：2009-01-01 00:00:00
abstract：:By taking advantage of the excessively upregulated expression of neuropilin (NRP) on the surface of both glioma cells and endothelial cells of angiogenic blood vessels, the ligand of NRP with high affinity - tLyp-1 peptide, which also contains a CendR motif ((R/K)XX(R/K)), was functionalized to the surface of PEG-PLA ...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/j.biomaterials.2013.04.025
更新日期：2013-07-01 00:00:00
abstract：:Ultra-high molecular-weight polyethylene (UHMWPE) has been used in total joint replacement for the last three decades. Despite the recent advancements in prosthesis design, the wear of UHMWPE remains a serious clinical problem; the release of wear debris may induce osteolysis and implant loosening. Controlling the qua...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/s0142-9612(03)00264-3
更新日期：2003-10-01 00:00:00
abstract：:Surface properties of poly (D,L-lactide) (PDLLA) were modified by combining plasma treatment and collagen modification. The changes of surface properties were characterized by contact angles, surface energy, X-ray photoelectron spectra and scanning electron microscopy. The mouse 3T3 fibroblasts were used as model cell...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/s0142-9612(01)00400-8
更新日期：2002-06-01 00:00:00
abstract：:A tissue-engineered substitute that facilitates large-volume regeneration of the subcutaneous adipose tissue layer is needed for reconstructive plastic surgery. Towards this goal, we describe the in vitro culture of primary human adipose-derived stem cells (ASC) seeded into placental decellular matrix (PDM) and cross-...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/j.biomaterials.2007.12.028
更新日期：2008-04-01 00:00:00
abstract：:A glucose biosensor was fabricated with loading of glucose oxidase (GOx) into a new organic-inorganic hybrid nanocomposite. The preparation involves formation of silica network into a Nafion (perfluorosulfonate ionomer) and subsequent loading of polyaniline grafted multiwalled carbon nanotubes (MWNT-g-PANI) onto Nafio...
journal_title：Biomaterials
pub_type： 杂志文章
doi：10.1016/j.biomaterials.2009.07.047
更新日期：2009-10-01 00:00:00
