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G-Quadruplex-Proximized Aptamers (G4PA) Efficiently Targeting Cell-Surface Transferrin Receptors for Targeted Cargo Delivery.

Yi DuQiwei WangLili ShiTao Li
Published in: Nano letters (2022)
DNA-assembled multiaptamer systems have been demonstrated to significantly promote the aptamer capacity of binding cell-surface-expressed proteins. However, how to conveniently harness them for efficient transmembrane delivery of targets remains a challenge. Toward this goal, here we engineer a G-quadruplex-proximized aptamer (G4PA) system in which a DNA aptamer specific for transferrin receptor (TfR) is guided by a bimolecular G4 and assembles into a dimerized proximity form that well matches homodimeric TfR highly expressed on the cancer cell surface. This system displays a higher capacity for targeting cell-surface TfR than the monomeric aptamer and super transmembrane transportation of nucleic acid cargoes, which is comparable to that of conventional liposome transfection but overcomes the lack of targeting ability of the latter. The G4PA system is then applied to the targeted delivery of siRNA for PLK1 gene silencing in positive cells rather than negative controls, showing great promise for use in precise anticancer therapy.
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