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

AUTHORS

Zhang Q , Jeppesen DK , Higginbotham JN , Graves-Deal R , Trinh VQ , Ramirez MA , Sohn Y , Neininger AC , Taneja N , McKinley ET , Niitsu H , Cao Z , Evans R , Glass SE , Ray KC , Fissell WH , Hill S , Rose KL , Huh WJ , Washington MK , Ayers GD , Burnette DT , Sharma S , Rome LH , Franklin JL , Lee YA , Liu Q , Coffey RJ , . Nature cell biology. 2021 12 09; 23(12). 1240-1254

PMID: 34887515 [PubMed].

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.