College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea..
Nanomedicine. 2020 Feb;24:102053. doi: 10.1016/j.nano.2019.102053. Epub 2019 Jul 22.
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负载 DNA 纳米结构，这些结构被包裹在聚多巴胺中，并通过与癌细胞靶向 DNA 适体非共价连接。初始 DNA 纳米结构通过滚环扩增和 Mu 肽缩合形成。这种 DNA 纳米结构装载了反义寡核苷酸、光增敏剂或抗癌化疗药物。然后，每种治疗剂负载的 DNA 纳米结构都被聚多巴胺（PDA）包裹，并通过与多聚腺嘌呤尾核酸适体（PA）非共价连接，该适体特异性针对 PTK7 受体，从而得到 PA 连接和 PDA 包裹的 DNA 纳米结构（PA/PDN）。PDA 涂层壳可实现光热疗法。在过度表达 PTK7 受体的细胞中，负载光增敏剂的 PA/PDN 表现出更高的光动力活性。与其他组相比，负载阿霉素的 PA/PDN 发挥了更高的抗癌活性。与其他组相比，负载反义寡核苷酸的 PA/PDN 可选择性降低靶蛋白。我们的结果表明，PA 连接和 PDA 包裹的 DNA 纳米结构可实现针对癌细胞的特定受体靶向光疗、化疗和基因治疗。
