1. Supermeres are functional extracellular nanoparticles replete with disease biomarkers and therapeutic targets
- Author
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Zhang, Qin, Jeppesen, Dennis K, Higginbotham, James N, Graves-Deal, Ramona, Trinh, Vincent Q, Ramirez, Marisol A, Sohn, Yoojin, Neininger, Abigail C, Taneja, Nilay, McKinley, Eliot T, Niitsu, Hiroaki, Cao, Zheng, Evans, Rachel, Glass, Sarah E, Ray, Kevin C, Fissell, William H, Hill, Salisha, Rose, Kristie Lindsey, Huh, Won Jae, Washington, Mary Kay, Ayers, Gregory Daniel, Burnette, Dylan T, Sharma, Shivani, Rome, Leonard H, Franklin, Jeffrey L, Lee, Youngmin A, Liu, Qi, and Coffey, Robert J
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,Bioengineering ,Rare Diseases ,Nanotechnology ,Orphan Drug ,Alzheimer's Disease ,Cancer ,Acquired Cognitive Impairment ,Dementia ,Aging ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Neurodegenerative ,Brain Disorders ,Development of treatments and therapeutic interventions ,Aetiology ,2.1 Biological and endogenous factors ,5.1 Pharmaceuticals ,Good Health and Well Being ,Alzheimer Disease ,Angiotensin-Converting Enzyme 2 ,Biological Transport ,Biomarkers ,COVID-19 ,Cardiovascular Diseases ,Cell Communication ,Cell Line ,Tumor ,Extracellular Vesicles ,HeLa Cells ,Humans ,Lactic Acid ,MicroRNAs ,Nanoparticles ,Neoplasms ,Tumor Microenvironment ,Hela Cells ,Medical and Health Sciences ,Developmental Biology ,Biochemistry and cell biology - Abstract
Extracellular vesicles and exomere nanoparticles are under intense investigation as sources of clinically relevant cargo. Here we report the discovery of a distinct extracellular nanoparticle, termed supermere. Supermeres are morphologically distinct from exomeres and display a markedly greater uptake in vivo compared with small extracellular vesicles and exomeres. The protein and RNA composition of supermeres differs from small extracellular vesicles and exomeres. Supermeres are highly enriched with cargo involved in multiple cancers (glycolytic enzymes, TGFBI, miR-1246, MET, GPC1 and AGO2), Alzheimer's disease (APP) and cardiovascular disease (ACE2, ACE and PCSK9). The majority of extracellular RNA is associated with supermeres rather than small extracellular vesicles and exomeres. Cancer-derived supermeres increase lactate secretion, transfer cetuximab resistance and decrease hepatic lipids and glycogen in vivo. This study identifies a distinct functional nanoparticle replete with potential circulating biomarkers and therapeutic targets for a host of human diseases.
- Published
- 2021