Development of an Aptamer-Conjugated Polyrotaxane-Based Biodegradable Magnetic Resonance Contrast Agent for Tumor-Targeted Imaging

Gadolinium-based magnetic resonance imaging (MRI) contrast agents with biodegradability, biosafety, and high efficiency are highly desirable for tumor diagnosis. Herein, a biodegradable, AS1411-conjugated, α-cyclodextrin polyrotaxane-based MRI contrast agent (AS1411-G2(DTPA-Gd)-SS-PR) was developed for targeted imaging of cancer. The polyrotaxane-based contrast agent was achieved by the complexation of α-cyclodextrin (α-CD) and a linear poly(ethylene glycol) (PEG) chain containing disulfide linkages at two terminals. The disulfides enable the dethreading of the polyrotaxane into excretable small units due to cleavage of the disulfide linkages by reducing agents such as intracellular glutathione (GSH). Furthermore, the second-generation lysine dendron conjugated with gadolinium chelates and AS1411, a G-quadruplex oligonucleotide that has high binding affinity to nucleolin generally presenting a high level on the surface of tumor cells, coupled to the α-CD via click chemistry. The longitudinal relaxivity of...