Metal-Organic Framework-Based Nanoplatform for Intracellular Environment-Responsive Endo/Lysosomal Escape and Enhanced Cancer Therapy

Abstract

Nowadays, efficient endo/lysosomal escape and the subsequent release of drugs into the cytosol are the major obstacles for nanoplatform-based cancer therapy. Herein, we first report a metal-organic framework-based nanoplatform (doxorubicin@ZIF-8@AS1411) for intracellular environment-responsive endo/lysosomal escape and enhanced cancer therapy. In our system, the nanoplatform was first targeted toward the cancer cells. Then, it was entrapped in endo/lysosomes, where pH-responsive decomposition occurred and abundant Zn ions were released. The released Zn ions could induce an influx of counterions, promote reactive singlet oxygen (ROS) generation to rupture the endo/lysosomal membrane, and accelerate the release of anticancer drugs in the cytosol. Finally, the released drugs and the generation of ROS could synergistically enhance cancer therapy. With excellent biocompatibility, effective endo/lysosomal escape, and enhanced therapeutic effect, the novel drug delivery systems are supposed to become a promising anticancer agent for cancer therapy and bring more opportunities for biomedical application.

Keywords: aptamer; cancer therapy; endo/lysosomal escape; intracellular environment-responsive; metal−organic frameworks.