ABSTRACT
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.
Subject(s)
DNA/chemistry , MicroRNAs/blood , Nucleic Acid Amplification Techniques/methods , Spectrometry, Fluorescence/methods , Benzothiazoles/chemistry , Biosensing Techniques/methods , Cell Line, Tumor , DNA/genetics , DNA Probes/chemistry , DNA Probes/genetics , Fluorescent Dyes/chemistry , G-Quadruplexes , Humans , Inverted Repeat Sequences , Limit of Detection , MicroRNAs/genetics , Nucleic Acid HybridizationABSTRACT
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
ABSTRACT
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.
