Laboratory for Formulation Research, Taiho Pharmaceutical Co., Ltd. , 224-2 Ebisuno, Hiraishi, Kawauchi-cho, Tokushima 771-0194, Japan.
ACS Nano. 2013 Sep 24;7(9):7534-41. doi: 10.1021/nn401317t. Epub 2013 Aug 21.
A system that permits the delivery of cargoes to the lung endothelium would be extraordinarily useful in terms of curing a wide variety of lung-related diseases. This study describes the development of a multifunctional envelope-type nanodevice (MEND) that targets the lung endothelium, delivers its encapsulated siRNA to the cytoplasm, and eradicates lung metastasis. The key to the success can be attributed to the presence of a surface-modified GALA peptide that has dual functions: targeting the sialic acid-terminated sugar chains on the pulmonary endothelium and subsequently delivering the encapsulated cargoes to the cytosol via endosomal membrane fusion, analogous to the influenza virus. The active targeting of MENDs without the formation of large aggregates was verified by intravital real-time confocal laser scanning microscopy in living lung tissue. The GALA-modified MEND is a promising carrier that opens a new generation of therapeutic approaches for satisfying unmet medical needs in curing lung diseases.
一种能够将货物递送到肺内皮的系统，在治疗各种与肺相关的疾病方面将非常有用。本研究描述了一种多功能信封型纳米器件（MEND）的开发，该纳米器件靶向肺内皮，将其包裹的 siRNA 递送到细胞质中，并根除肺转移。成功的关键可以归因于表面修饰的 GALA 肽的存在，该肽具有双重功能：靶向肺内皮上末端为唾液酸的糖链，随后通过内体膜融合将包裹的货物递送到细胞质中，类似于流感病毒。通过活体实时共聚焦激光扫描显微镜在活体肺组织中验证了 MEND 无大聚集体形成的主动靶向。GALA 修饰的 MEND 是一种很有前途的载体，为满足治疗肺部疾病方面未满足的医疗需求开辟了新一代治疗方法。
