Engineering of Switchable Aptamer Micelle Flares for Molecular Imaging in Living Cells

Simultaneous monitoring of the expression, distribution, and dynamics of biological molecules in living cells is one of the most challenging tasks in the analytical sciences. The key to effective and successful intracellular imaging is the development of delivery platforms with high efficiency and ultrasensitive molecular probes for specific targets of interest. To achieve these goals, many nanomaterials are widely used as carriers to introduce nucleic acid probes into living cells for real-time imaging of biomolecules. However, limitations on their use include issues of cytotoxicity and delivery efficiency. Herein, we propose a switchable aptamer micelle flare (SAME), formed by self-assembly of an aptamer switch probe-diacyllipid chimera, to monitor ATP molecules inside living cells. Similarity of hydrophobic composition between diacyllipids in the micelle flares and phospholipid bilayers in the dynamic membranes of living cells allows SAMFs to be uptaken by living cells more efficiently than aptamer switch probes without external auxiliary. Switchable aptamers were found to bind target ATP molecules with high selectivity and specificity, resulting in restoration of the fluorescence signal from OFF to ON state, thus indicating the presence of the analyte. These switchable aptamer micelle flares, which exhibit cell permeability and nanoscale controllability, show exceptional promise for molecular imaging in bioanalysis, disease diagnosis, and drug delivery.