DPA‐Zinc around Polyplexes Acts Like PEG to Reduce Protein Binding While Targeting Cancer Cells

• Published in: Advanced healthcare materials Vol. 12; no. 21; pp. e2203252 - n/a
• Main Authors: Nie, Xuan, You, Wei, Zhang, Ze, Gao, Fan, Zhou, Xiao‐Hong, Wang, Hai‐Li, Wang, Long‐Hai, Chen, Guang, Wang, Chang‐Hui, Hong, Chun‐Yan, Shao, Qi, Wang, Fei, Xia, Lei, Li, Yang, You, Ye‐Zi
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.08.2023
• Subjects: Anions; Binding; Cancer; Cationic polymerization; dipicolylamine‐zinc; Entrapment; gene delivery; Gene therapy; Hydration; hydration water layers; Nanoparticles; Protein adsorption; Proteins; Sheaths; targeting cancer cells; Transfection; Zinc; gene delivery; hydration water layers; dipicolylamine-zinc; targeting cancer cells
• ISSN: 2192-2640; 2192-2659; 2192-2659
• DOI: 10.1002/adhm.202203252

Gene therapy holds great promise as an effective treatment for many diseases of genetic origin. Gene therapy works by employing cationic polymers, liposomes, and nanoparticles to condense DNA into polyplexes via electronic interactions. Then, a therapeutic gene is introduced into target cells, thereby restoring or changing cellular function. However, gene transfection efficiency remains low in vivo due to high protein binding, poor targeting ability, and substantial endosomal entrapment. Artificial sheaths containing PEG, anions, or zwitterions can be introduced onto the surface of gene carriers to prevent interaction with proteins; however, they reduce the cellular uptake efficacy, endosomal escape, targeting ability, thereby, lowering gene transfection. Here, it is reported that linking dipicolylamine‐zinc (DPA‐Zn) ions onto polyplex nanoparticles can produce a strong hydration water layer around the polyplex, mimicking the function of PEGylation to reduce protein binding while targeting cancer cells, augmenting cellular uptake and endosomal escape. The polyplexes with a strong hydration water layer on the surface can achieve a high gene transfection even in a 50% serum environment. This strategy provides a new solution for preventing protein adsorption while improving cellular uptake and endosomal escape. Linking dipicolylamine‐zinc ions onto the polyplex can construct a strong hydration water layer around the polyplex, which can not only reduce protein adsorption but also enhance the tumor target, cellular uptake, and endosomal escape activity due to the strong interaction with phosphatidylserine from the tumor cells, resulting in high gene delivery efficacy in serum‐containing environments.