Here, we report various therapeutic cargo-loadable DNA nanostructures that are shelled in polydopamine and noncovalently tethered with cancer cell-targeting DNA aptamers. Initial DNA nanostructure was formed by rolling-circle amplification and condensation with Mu peptides. This DNA nanostructure was loaded with an antisense oligonucleotide, a photosensitizer, or an anticancer chemotherapeutic drug. Each therapeutic agent-loaded DNA nanostructure was then shelled with polydopamine (PDA), and noncovalently decorated with a poly adenine-tailed nucleic acid aptamer (PA) specific for PTK7 receptor, resulting in PA-tethered and PDA-shelled DNA nanostructure (PA/PDN). PDA coating shell enabled photothermal therapy. In the cells overexpressing PTK7 receptor, photosensitizer-loaded PA/PDN showed greater photodynamic activity. Doxorubicin-loaded PA/PDN exerted higher anticancer activity than the other groups. Antisense oligonucleotide-loaded PA/PDN provided selective reduction of target proteins compared with other groups. Our results suggest that the PA-tethered and PDA-shelled DNA nanostructures could enable the specific receptor-targeted phototherapy, chemotherapy, and gene therapy against cancer cells.

在这里，我们报告了各种治疗性货物可装载的DNA纳米结构，它们被装在聚多巴胺中，并与靶向癌细胞的DNA适体非共价连接。最初的DNA纳米结构是通过滚环扩增和与Mu肽的缩合形成的。该DNA纳米结构中装有反义寡核苷酸，光敏剂或抗癌化疗药物。然后，将每个装载有治疗剂的DNA纳米结构用聚多巴胺（PDA）脱壳，并用对PTK7受体特异的聚腺嘌呤尾核酸适体（PA）非共价修饰，从而形成由PA束缚和带有PDA壳的DNA纳米结构（PA / PDN）。PDA涂层外壳实现了光热疗法。在过度表达PTK7受体的细胞中，光敏剂负载的PA / PDN表现出更大的光动力活性。负载阿霉素的PA / PDN的抗癌活性高于其他组。与其他组相比，负载反义寡核苷酸的PA / PDN选择性降低了目标蛋白。我们的研究结果表明，PA系链和PDA外壳的DNA纳米结构可以实现针对癌细胞的特异性受体靶向光疗，化学疗法和基因疗法。