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.