Multimodal Detection of a Small Molecule Target Using Stimuli-Responsive Liposome Triggered by Aptamer–Enzyme Conjugate

[Image: see text] Nanomaterials which can respond to external stimuli have attracted considerable attention due to their potential applications in sensing and biomedicine. One of the most promising classes of such materials is the stimuli-responsive liposome that can release its contents in response to a specific target. Despite recent progress, development of liposomes responsive to small molecular targets remains a challenge, due to the difficulty in designing the transduction process to link between target binding and triggered release, even though small molecular metabolites play important roles in many biological processes. Herein, we demonstrate a combination of an aptamer (apt) for target recognition and enzyme phosphatidylcholine 2-acetylhydrolase (PLA(2)) for rupture of liposome. As a proof-of-concept, cocaine molecules were used to trigger the release of the enzyme. The exposure to DNA–PLA(2) conjugates induced the rupture of liposome containing uranin and gadopentetic acid (Gd-DTPA), allowing multimodal fluorescent and MRI detection of cocaine. The strategy demonstrated in this work can be generally applied to other imaging modalities by loading different imaging agents, as well as other targets by using different functional DNAs.