Targeting extracellular vesicles to injured tissue using membrane cloaking and surface display
| العنوان: | Targeting extracellular vesicles to injured tissue using membrane cloaking and surface display |
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| المؤلفون: | Ryan Middleton, Kiel Peck, Jackie Valle, Travis J. Antes, Eduardo Marbán, Kristin Luther, Antonio Echavez, Weixin Jane Liu, Takeshi Ijichi |
| المصدر: | Journal of Nanobiotechnology, Vol 16, Iss 1, Pp 1-15 (2018) Journal of Nanobiotechnology |
| بيانات النشر: | BMC, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Targeting antibodies, Pharmaceutical Science, Medicine (miscellaneous), Cloaking, Ischemia/reperfusion injury, Exosomes, Rats, Inbred WKY, Applied Microbiology and Biotechnology, Polyethylene Glycols, Myoblasts, Rats, Sprague-Dawley, chemistry.chemical_compound, Biodistribution, Tissue Distribution, Molecular Targeted Therapy, Homing peptides, Phospholipids, Qdots, Cardiomyocytes, Chemistry, Vesicle, Optical Imaging, Extracellular vesicles, Phospholipid, lcsh:R855-855.5, Infarction, NanoSight NTA, Biotinylation, Molecular Medicine, Female, Signal Transduction, Streptavidin, lcsh:Medical technology, Surface Properties, lcsh:Biotechnology, Biomedical Engineering, Biotin, Bioengineering, Exosome, Antibodies, Cell Line, 03 medical and health sciences, lcsh:TP248.13-248.65, Quantum Dots, Animals, Humans, Secretion, C1C2 domain fusions, Particle Size, Fluorescent Dyes, Research, Biological Transport, Surface display, Microvesicles, Rats, Lactadherin, 030104 developmental biology, Biophysics, Membrane anchor, Nanoparticles, Peptides, Homing (hematopoietic), EV |
| الوصف: | Background Extracellular vesicles (EVs) and exosomes are nano-sized, membrane-bound vesicles shed by most eukaryotic cells studied to date. EVs play key signaling roles in cellular development, cancer metastasis, immune modulation and tissue regeneration. Attempts to modify exosomes to increase their targeting efficiency to specific tissue types are still in their infancy. Here we describe an EV membrane anchoring platform termed “cloaking” to directly embed tissue-specific antibodies or homing peptides on EV membrane surfaces ex vivo for enhanced vesicle uptake in cells of interest. The cloaking system consists of three components: DMPE phospholipid membrane anchor, polyethylene glycol spacer and a conjugated streptavidin platform molecule, to which any biotinylated molecule can be coupled for EV decoration. Results We demonstrate the utility of membrane surface engineering and biodistribution tracking with this technology along with targeting EVs for enhanced uptake in cardiac fibroblasts, myoblasts and ischemic myocardium using combinations of fluorescent tags, tissue-targeting antibodies and homing peptide surface cloaks. We compare cloaking to a complementary approach, surface display, in which parental cells are engineered to secrete EVs with fusion surface targeting proteins. Conclusions EV targeting can be enhanced both by cloaking and by surface display; the former entails chemical modification of preformed EVs, while the latter requires genetic modification of the parent cells. Reduction to practice of the cloaking approach, using several different EV surface modifications to target distinct cells and tissues, supports the notion of cloaking as a platform technology. Electronic supplementary material The online version of this article (10.1186/s12951-018-0388-4) contains supplementary material, which is available to authorized users. |
| اللغة: | English |
| تدمد: | 1477-3155 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0757f9ab6784cead77c7b1e4c0522bb3Test http://link.springer.com/article/10.1186/s12951-018-0388-4Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0757f9ab6784cead77c7b1e4c0522bb3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14773155 |
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