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.

中文翻译：

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G-四链体接近适体 (G4PA) 有效靶向细胞表面转铁蛋白受体，用于靶向货物递送

DNA 组装的多适体系统已被证明可显着提高结合细胞表面表达的蛋白质的适体能力。然而，如何方便地利用它们来有效地跨膜传递目标仍然是一个挑战。为实现这一目标，我们在此设计了一个 G-四链体接近适体 (G4PA) 系统，其中转铁蛋白受体 (TfR) 特异的 DNA 适体由双分子 G4 引导并组装成与高表达同源二聚体 TfR 匹配的二聚邻近形式在癌细胞表面。该系统比单体适体和核酸货物的超跨膜转运具有更高的靶向细胞表面TfR的能力，与传统的脂质体转染相当，但克服了后者靶向能力的不足。