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.

Achieving efficient and safe gene delivery is of great significance to promote the development of gene therapy. In this work, a polydopamine (PDA) layer was coated on the surface of Fe3O4 nanoparticles (NPs) by dopamine (DA) self‐polymerization, and then magnetic Fe3O4 NPs were prepared by the Michael addition between amino groups in polyethyleneimine (PEI) and PDA. The prepared Fe3O4 NPs (named Fe3O4@PDA@PEI) were characterized by Fourier transform infrared (FTIR), atomic force microscopy (AFM), and scanning electron microscopy (SEM). As an efficient and safe gene carrier, the potential of Fe3O4@PDA@PEI was evaluated by agarose gel electrophoresis, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay, fluorescence microscopy, and flow cytometry. The results show that the Fe3O4@PDA@PEI NPs are stable hydrophilic NPs with a particle size of 50–150 nm. It can efficiently condense DNA at low N/P ratios and protect it from nuclease degradation. In addition, the Fe3O4@PDA@PEI NPs have higher safety than PEI. Further, the Fe3O4@PDA@PEI/DNA polyplexes could be effectively absorbed by cells and successfully transfected and exhibit higher cellular uptake and gene transfection efficiency than PEI/DNA polyplexes. The findings indicate that the Fe3O4@PDA@PEI NPs have the potential to be developed into a novel gene vector.

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Fe 3 O 4 nanoparticles (NPs) are widely used in the construction of drug and gene delivery vectors because of their particular physicochemical properties. Surface modification can not only reduce the cytotoxicity of Fe 3 O 4 , but also further improve the biocompatibility and delivery efficiency. In this work, firstly, polydopamine (PDA)-coated Fe 3 O 4 NPs (named Fe 3 O 4 @PDA) were prepared by using the selfpolymerization characteristics of dopamine in alkaline environment. Then, polyamidoamine (PAMAM) was modified by the Michael addition reaction to prepare water-soluble core-shell magnetic NPs of Fe 3 O 4 @PDA@PAMAM, and its potential as gene vector was further evaluated. The results revealed that Fe 3 O 4 @PDA@PAMAM had the ability to condense and protect DNA, and showed lower cytotoxicity, higher cell uptake and transfection efficiency than those of PAMAM. It has the potential to become a magnetic targeted gene vector for further study.