RESUMO
A functionalized dumbbell probe (FDP) based amplification method, termed as a cascading exponential amplification DNA machine (CEA-DNA machine), has been developed to autonomously accumulate single G-quadruplexes (SGQs) and twin-G-quadruplexes (TGQs) for robust fluorescence signal-on probing of miRNA-21.
Assuntos
DNA/química , MicroRNAs/sangue , Técnicas de Amplificação de Ácido Nucleico/métodos , Espectrometria de Fluorescência/métodos , Benzotiazóis/química , Técnicas Biossensoriais/métodos , Linhagem Celular Tumoral , DNA/genética , Sondas de DNA/química , Sondas de DNA/genética , Corantes Fluorescentes/química , Quadruplex G , Humanos , Sequências Repetidas Invertidas , Limite de Detecção , MicroRNAs/genética , Hibridização de Ácido NucleicoRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMO
There are disease-causing biohazards in the blood that cannot be treated with modern medicines. Here we show that an intelligently designed safe biomaterial can precisely identify, tow and dump a targeted biohazard from the blood into the small intestine. Positively charged mesoporous silica nanoparticles (MSNs) functionalized with EGFR-targeting aptamers (MSN-AP) specifically recognize and bind blood-borne negatively charged oncogenic exosomes (A-Exo), and tow A-Exo across hepatobiliary layers and Oddi's sphincter into the small intestine. MSN-AP specifically distinguish and bind A-Exo from interfering exosomes in cell culture and rat and patient blood to form MSN-AP and A-Exo conjugates (MSN-Exo) that transverse hepatocytes, cholangiocytes, and endothelial monolayers via endocytosis and exocytosis mechanisms, although Kupffer cells have been shown to engulf some MSN-Exo. Blood MSN-AP significantly decreased circulating A-Exo levels, sequentially increased intestinal A-Exo and attenuated A-Exo-induced lung metastasis in mice. This study opens an innovative avenue to relocate blood-borne life-threatening biohazards to the intestine.