Preparation and characterization of an amylase-triggered dextrin-linked graphene oxide anticancer drug nanocarrier and its vascular permeability

We synthesized a dextrin (DEX)-conjugated graphene oxide (GO) nanocarrier (GO(100)-DEX) as a potential drug delivery system to respond to a tumor-associated stimulus, a-amylase, that has high permeability through the fenestrated endothelial barrier to the tumor site. At acidic pH and in the presence of alpha-amylase to simulate tumor conditions, GO(100)-DEX released a 1.5-fold higher amount of doxorubicin (DOX) than of GO(100). Under the same conditions, the cytotoxic effects of GO(100)-DEX/DOX were 2-fold greater than those of free DOX and 2.9-fold greater than those of GO(100)/DOX. Employing an in vitro biomimetic microfluidic blood vessel model lined with human umbilical vein endothelial cells, we evaluated the tumor vasculature endothelial permeation of GO(100)-DEX and GO(100) using dextrans of 10 and 70 kDa for comparison and as standards to validate the microfluidic blood vessel model. The results showed that the permeabilities of GO(100)-DEX and GO(100) were 4.3- and 4.9-fold greater than that of 70 kDa dextran and 2.7-and 3.1-fold higher than that of 10 kDa dextran, thus demonstrating the good permeability of the GO-based nanocarrier through the fenestrated endothelial barrier.