DNA纳米机器药物递送研究进展

Drug delivery based on DNA nanorobots

天然分子机器是细胞正常功能(包括DNA复制、细胞内物质运输、离子平衡和细胞运动等)的重要执行者。受天然分子机器的启发,人工分子机器的概念被提出并逐步实践。DNA分子独特的理化性质使得其可作为自组装基元用于构建分子机器类纳米结构。DNA纳米结构具有形状可设计性、精确的可寻址性、结构动态响应性及良好的生物相容性,可以作为一种良好的药物递送载体材料。通过可寻址的负载特定功能元件从而构建DNA纳米载体和治疗型DNA纳米机器,可以靶向性地将药物传递到病变组织和细胞,响应性地释放药物,提高药物的细胞摄取率并降低其毒副作用,有望成为优秀的药物递送系统。基于DNA纳米结构的药物载体已经被用于递送小分子药物、寡核苷酸类药物和蛋白药物。以每类药物分子中的典型药物为例,介绍了DNA纳米载体和DNA纳米机器药物递送系统的研究进展,并讨论了其所面临的挑战及可能的发展趋势。

Natural mechanical devices carry out critical tasks for cell function,including DNA replication,intracellular transport,ion pumping and cell motility.Inspired by nature,artificial devices and machines on the molecular scale have been bottom-up designed, constructed,and operated.The unique chemical and physical properties enable DNA molecules to serve as building blocks to construct artificial,machine-like nanostructures.DNA nanostructures are characteristic of the uniform sizes and shapes,precise spatial addressability and reconfigurable mechanical operation as well as excellent biocumpatibility,showing great promise for drug delivery.After integrating specific functional moieties on addressable structures,therapeutic DNA nanorobots have been constructed,which can deliver cargoes to target diseased cells or region,responsively release the loaded drugs and enhance the therapeutic efficacy.The molecular cargoes attached to DNA-based nanocarriers are usually three types:small molecular drugs,functional oligonucleotides,and therapeutic proteins.In this review,recent advances of DNA nanocarriers and therapeutic nanorobots for intelligent drug delivery are summarized.The challenges and future perspectives regarding functional DNA materials are discussed.