Effect of Extracellular Matrix Coating on Cancer Cell Membrane-Encapsulated Polyethyleneimine/DNA Complexes for Efficient and Targeted DNA Delivery In Vitro.

Polyethyleneimine (PEI) has a good spongy proton effect and is an excellent nonviral gene vector, but its high charge density leads to the instability and toxicity of PEI/DNA complexes. Cell membrane (CM) capsules provide a universal and natural solution for this problem. Here, CM-coated PEI/DNA capsules (CPDcs) were prepared through extrusion, and the extracellular matrix was coated on CPDcs (ECM-CPDcs) for improved targeting. The results showed that compared with PEI/DNA complexes, CPDcs had core-shell structures (PEI/DNA complexes were coated by a 6-10 nm layer), lower cytotoxicity, and obvious homologous targeting. The internalization and transfection efficiency of 293T-CM-coated PEI70k/DNA capsules (293T-CP70Dcs) were 91.8 and 74.5%, respectively, which were higher than those of PEI70k/DNA complexes. Then, the internalization and transfection efficiency of 293T-CP70Dcs were further improved by ECM coating, which were 94.7 and 78.9%, respectively. Then, the internalization and transfection efficiency of 293T-CP70Dcs were further improved by ECM coating, which were 94.7 and 78.9%, respectively. Moreover, the homologous targeting of various CPDcs was improved by ECM coating, and other CPDcs also showed similar effects as 293T-CP70Dcs after ECM coating. These findings suggest that tumor-targeted CPDcs may have considerable advantages in gene delivery.