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

Abstract

We synthesized a dextrin (DEX)-conjugated graphene oxide (GO) nanocarrier (GO₁₀₀-DEX) as a potential drug delivery system to respond to a tumor-associated stimulus, α-amylase, that has high permeability through the fenestrated endothelial barrier to the tumor site. At acidic pH and in the presence of α-amylase to simulate tumor conditions, GO₁₀₀-DEX released a 1.5-fold higher amount of doxorubicin (DOX) than of GO₁₀₀. Under the same conditions, the cytotoxic effects of GO₁₀₀-DEX/DOX were 2-fold greater than those of free DOX and 2.9-fold greater than those of GO₁₀₀/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 GO₁₀₀-DEX and GO₁₀₀ using dextrans of 10 and 70kDa for comparison and as standards to validate the microfluidic blood vessel model. The results showed that the permeabilities of GO₁₀₀-DEX and GO₁₀₀ were 4.3- and 4.9-fold greater than that of 70kDa dextran and 2.7- and 3.1-fold higher than that of 10kDa dextran, thus demonstrating the good permeability of the GO-based nanocarrier through the fenestrated endothelial barrier.

Keywords: Dextrin; Graphene oxide; Microfluidic device; Triggered release; Vascular permeability; α-amylase.