Belting Mattias, Sandgren Staffan, Wittrup Anders
Lund University, BMC, C-13, SE-221 84 Lund, Sweden.
Adv Drug Deliv Rev. 2005 Feb 28;57(4):505-27. doi: 10.1016/j.addr.2004.10.004. Epub 2004 Dec 28.
Recent evidence for efficient delivery of macromolecules, such as peptides and nucleic acids, from the cell exterior to the nucleus offers the interesting possibility of developing novel treatments directed at intranuclear targets. The findings should also stimulate the search for physiological ligands that utilize similar transport mechanisms to regulate pathobiological processes. Cytokines, growth factors and their receptors, as well as morphogens have all been shown to enter the nucleus to evoke biological responses in target cells. The rational design of intracellular drug delivery vehicles requires an increased understanding of the elaborate systems that mediate cellular communication and coordination with the extracellular environment without inflicting on the integrity of the cell. This review discusses some aspects of the carriers and barriers in macromolecular transport.
最近有证据表明,诸如肽和核酸等大分子能够有效地从细胞外部传递至细胞核,这为开发针对核内靶点的新型治疗方法提供了有趣的可能性。这些发现还应促使人们寻找利用类似转运机制来调节病理生物学过程的生理配体。细胞因子、生长因子及其受体以及形态发生素均已被证明可进入细胞核,从而在靶细胞中引发生物学反应。合理设计细胞内药物递送载体需要更深入地了解那些介导细胞与细胞外环境进行通讯和协调且不会损害细胞完整性的精细系统。本综述讨论了大分子运输中的一些载体和屏障方面的内容。