The Application of Stimuli-Responsive VEGF- and ATP-Aptamer-Based Microcapsules for the Controlled Release of an Anticancer Drug, and the Selective Targeted Cytotoxicity toward Cancer Cells

摘要

The synthesis of microcapsules consisting of DNA shells crosslinked by anti-VEGF (vascular epithelial growth factor) or anti-ATP (adenosine triphosphate) aptamers and loaded with tetramethylrhodamine-modified dextran, TMR-D, and Texas Red-modified dextran, TR-D, respectively, as fluorescence labels acting as models for drug loads, is described. The aptamer-functionalized microcapsules act as stimuli-responsive carriers for the triggered release of the fluorescent labels in the presence of the overexpressed cancer cell biomarkers VEGF or ATP. The VEGF- and ATP-responsive microcapsules are, also, loaded with the anticancer drug doxorubicin (DOX), in the form of DOX-functionalized dextran, DOX-D. The release of DOX-D from the respective microcapsules proceeds in the presence of VEGF or ATP as triggers. Preliminary cell experiments reveal that the ATP-responsive DOX-D-loaded microcapsules undergo effective endocytosis into MDA-MB-231 cancer cells. The ATP-responsive DOX-D-loaded microcapsules incorporated into the MDA-MB-231 cancer cells reveal impressive cytotoxicity as compared to normal epithelial MCF-10A breast cells (50% vs 0% cell death after 24 h, respectively). The cytotoxicity of the ATP-responsive DOX-D-loaded microcapsules toward the cancer cells is attributed to the effective unlocking of the microcapsules by overexpressed ATP, and to the subsequent release of DOX from the dextran backbone under acidic conditions present in cancer cells (pH = 6.2).