中文摘要
细胞超分子囊泡(exosome)是细胞间传递和交换信息的重要微粒,其粒径仅为30~100 nm,使其具备了成为内源性纳米载体的可能。Exosome可通过与目标细胞膜融合,在神经细胞指令下精确控制传递位置,从而实现主动靶向。Exosome 还具有可避免非宿主巨噬细胞吞噬、无细胞累积毒性等特点。青藤碱(Sinomenine,SIN)是从中药青藤中提取的抗肝癌活性成分,本课题拟以人肝源干细胞分泌的exosome 负载SIN,进行体内药动学及体内外肝靶向评价。从整体、细胞与分子水平三个层次,探讨exosome 定向传递SIN 进入癌细胞的可能性,有望为新型肝靶向载体的研究开辟新思路、新方法,并促进生物纳米技术在中药现代化中的应用。
英文摘要
Cellular exosomes are vesicular plasma membrane fragments with a diameter of 30–100 nanometres that are shed by cells in response to various physiological and artificial stimuli. Here we demonstrate that cell-derived microparticles can be used as vectors to deliver chemotherapeutic drugs. We show that tumour cells incubated with chemotherapeutic drugs package these drugs into microparticles, which can be collected and used to effectively kill tumour cells in murine tumour models without typical side effects. We describe several mechanisms involved in this process, including uptake of drug-containing microparticles by tumour cells, synthesis of additional drug-packaging microparticles by these cells that contribute to the cytotoxic effect and the inhibition of drug efflux from tumour cells. This study highlights a novel drug delivery strategy with potential clinical application.
