靶向活性的纳米载体可以显着改善水溶性差或生物大分子药物跨生物屏障的转运作用。然而，改进的原因还不够清楚，这阻碍了活性靶向纳米载体的合理设计。为了说明不同因素如何影响靶向活性纳米载体的转运，我们建立了针对不同受体的配体修饰的微团，通过比较内吞作用，转运途径和胞吐过程，研究了装饰物如何影响微团的胞吞作用。

选择了三种不同的受体，即新生儿Fc受体（FcRn），转铁蛋白受体（TfR）和αvβ3受体。他们提出了三种不同的转运途径，分别主要介导转胞吞作用，再循环途径和细胞结合。首先制备了具有不同配体密度的相应配体FcBP，7pep和c（RGDfK）装饰的胶束。然后研究了受体和配体密度对跨生物屏障转座作用的影响。

结果表明，活性胶束的吸收率高于被动胶束，并且在所有功能胶束中均出现了具有最多内吞作用的最佳配体密度。转运途径研究表明，将7pep修饰的胶束转移到顶端回收内体（ARE）中，并以配体依赖的方式胞吐至顶端质膜。c（RGDfK）修饰的胶束通过常见的回收内体（CRE）和高尔基复合体转移至基底外侧质膜而不是ARE。虽然FcBP修饰的胶束通过CRE吸收了回收途径和胞吞作用，但没有通过高尔基复合体。适当的配体密度（不是越高越好）导致吸收最多。顶端与基底外侧的胞吞作用之比也可能与摄取量不符。在所有行程中 通过CRE进行胞吞是进行胞吞的最佳路线。因此，在设计主动靶向纳米载体以克服生物学障碍时，应先考虑受体特性，然后优化配体密度。

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Active-targeting nanocarriers can significantly improve the transcytosis of poorly water-soluble or bio-macromolecular drugs across biological barrier. However, reasons for the improvement are not understood enough, which hampered the reasonable design of active targeting nanocarriers. To illustrate how different factors influence the transport of active-targeting nanocarriers, we established ligand-decorated micelles targeting different receptors to study how the decorations influence the transcytosis of the micelles by comparing the endocytosis, transport pathway and exocytosis process.

Three different kinds of receptors, Neonatal Fc receptor (FcRn), transferrin receptor (TfR) and αvβ3 receptor were selected. They presented three different transport pathways, mainly mediate transcytosis, recycling pathway and cell binding, respectively. Their corresponding ligand FcBP, 7pep and c(RGDfK) decorated micelles with different ligand densities were prepared first. Then the effects of receptor and ligand density on the transcytosis across biological barrier were investigated.

The results showed that the uptake rate of active micelles was higher than passive micelles and an optimum ligand density with most endocytosis appeared in all functional micelles. Transport pathway study showed 7pep decorated micelles transferred into apical recycling endosome (ARE) and exocytosed to apical plasma membrane in a ligand depended way. c(RGDfK) decorated micelles transferred through common recycling endosome (CRE) and Golgi complex to basolateral plasma membrane instead of ARE. While FcBP decorated micelles took both the recycling pathway and transcytosis through CRE, but not Golgi complex. Proper ligand density, not the higher the better, led the most uptake. Also the apical to basolateral transcytosis ratio may not be in accordance with the uptake. Among all the itineraries, transcytosis through CRE is the best itinerary for transcytosis. So, in the design of active targeting nanocarriers to overcome biological barrier, receptor character should be considered priorly, and then ligand density should be optimized.