We have developed a novel, nanosized drug carrier with high‐therapeutic payload, controllable release, and the potential for active tumor targeting. It consists of a 15 nm gold nanoparticle with dense surface loading of DNA duplexes. We utilize the natural intercalating behavior of daunomycin to load the drug between DNA base pairs. We obtained a high‐therapeutic payload of >1,000 drug molecules per gold nanoparticle (AuNP), one of the highest loadings reported in literature to date. We have engineered unique DNA sequences to control release of daunomycin for over 48 hr and show higher cell death compared to equivalent concentrations of free daunomycin. We have also explored cell internalization mechanisms to identify the pathways by which our gold nanoparticles enter the cell. This nanocarrier is in the ideal size range of 16–100 nm in diameter to utilize the enhanced permeability and retention effect for passive targeting to tumors. Our AuNP platform is effective as a therapeutic drug delivery device and can easily incorporate any aptamer of choice through complementary base pairing. Our work has produced an innovative nanoscale drug‐delivery platform potentially leading to personalized cancer therapies through careful selection of aptamers and an adjustable drug release profile.

中文翻译：

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核酸生物杂化纳米载体具有高治疗有效载荷和道诺霉素可控缓释用于癌症治疗

我们开发了一种新型纳米级药物载体，具有高治疗有效载荷、可控释放和主动肿瘤靶向潜力。它由 15 nm 金纳米粒子组成，表面负载密集的 DNA 双链体。我们利用道诺霉素的自然嵌入行为在 DNA 碱基对之间加载药物。我们获得了每个金纳米颗粒 (AuNP) > 1,000 个药物分子的高治疗载荷，这是迄今为止文献报道的最高载荷之一。我们设计了独特的 DNA 序列来控制道诺霉素的释放超过 48 小时，并且与同等浓度的游离道诺霉素相比，显示出更高的细胞死亡。我们还探索了细胞内化机制，以确定我们的金纳米粒子进入细胞的途径。这种纳米载体的直径在 16-100 nm 的理想尺寸范围内，可利用增强的渗透性和保留效应来被动靶向肿瘤。我们的 AuNP 平台作为治疗药物输送装置是有效的，并且可以通过互补碱基配对轻松整合任何选择的适体。我们的工作已经产生了一个创新的纳米级药物递送平台，通过仔细选择适体和可调节的药物释放曲线，可能会导致个性化的癌症治疗。