Safe and efficient DNA delivery based on tannic acid-ion coordination encapsulation

ABSTRACT Polyethyleneimine (PEI) is a non-viral gene vector of frequent concern because of its high transfection efficiency. However, its clinical application is limited by the cytotoxicity caused by high positive charge density. Therefore, reducing toxicity and maintaining high transfection efficiency through appropriate strategies are of great significance to promote the development of PEI as gene vector. In order to reduce the toxicity of PEI, this work studied the feasibility of encapsulating PEI/DNA complexes by using the coordination between tannic acid (TA) and metal ions (Mn+). Firstly, TA formed a coating layer on the surface of PEI/DNA complex through electrostatic action, and then the quaternary complex (Mn+(TA/PEI/DNA)) system was prepared by the coordination between metal ions and TA. In order to better construct a gene delivery system with high transfection efficiency and low toxicity, the effects of PEI molecular weight, mass ratio of PEI/DNA, mass ratio of TA, and types of metal ions on the transfection efficiency, cytotoxicity, particle size, zeta potential, and cell uptake pathway of the quaternary complex were studied. The results showed that the quaternary complex based on PEI70k and encapsulated by coordination between TA and potassium ions showed better safety than PEI70k/DNA while maintaining high transfection efficiency. This showed that the strategy of coordination encapsulation of TA and ions to improve the safety of PEI as gene carrier is feasible, which provides a new reference for the design of gene delivery system based on PEI.