Supermeres are functional extracellular nanoparticles replete with disease biomarkers and therapeutic targets

Nat Cell Biol. 2021 Dec;23(12):1240-1254. doi: 10.1038/s41556-021-00805-8. Epub 2021 Dec 9.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / pathology
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Biological Transport / physiology
  • Biomarkers / metabolism
  • COVID-19 / pathology
  • Cardiovascular Diseases / pathology
  • Cell Communication / physiology
  • Cell Line, Tumor
  • Extracellular Vesicles / metabolism*
  • HeLa Cells
  • Humans
  • Lactic Acid / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Nanoparticles / classification
  • Nanoparticles / metabolism*
  • Neoplasms / pathology
  • Tumor Microenvironment


  • Biomarkers
  • MicroRNAs
  • Lactic Acid
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2