Enhancing Deoxyribonucleic Acid Delivery Efficiency via pH-Responsive Metal-Tannic Acid Cross-Linking Encapsulation

Gene therapy is the treatment of diseases by introducing therapeutic genes into diseased cells. An effective gene delivery system is essential to the success of gene therapy. However, the rapid release of vector genes, especially the precise control of the transmission and release process of the vector in the subcellular structure, is still a major challenge. Here, we have successfully prepared a pH-responsive nanogene vector M^<i>n</i>+-TA/PEI by modifying polyethylenimine with metal ions and tannic acid. The particle sizes of Al³⁺-TA/PEI and Fe³⁺-TA/PEI changed significantly by adjusting the pH value. The property can realize the effective delivery and rapid release of genes according to changes in the environment <i>in vivo</i>, providing the possibility for its application in the acidic tumor microenvironment. Two vectors exhibited extremely low cytotoxicity, hemolysis, and protein absorption, which were easily uptaken by cells and could effectively promote gene expression. As expected, M^<i>n</i>+-TA/PEI has excellent DNA delivery ability and good safety, showing good application potential in gene delivery vectors.