Abstract

Nonionic surfactant, tetraethylene glycol monododecyl ether (C12EO4), cannot compact DNA because of its low efficiency in neutralizing the negative charges of the phosphate groups of DNA. It is also well-known that nonionic surfactants as a decompaction agent can help DNA be released from cationic surfactant aggregates. Herein, with the “bridge” Fe3+ of C12EO4, we found that C12EO4 can efficiently compact DNA molecules into globular states with a narrow size distribution, indicating that the cooperative Fe3+ can transform C12EO4 molecules from decompaction agents to compaction ones. The mechanism of the interaction of DNA and C12EO4 by “bridge” Fe3+ is that the Fe3+-C12EO4 complexes act as multivalent ions by cooperative and hydrophobic interaction. The improved colloidal-stability and endosome escape effect induced by C12EO4 would provide the potential applications of nonionic surfactant in the physiological characteristics of DNA complexes. Cell viability assay demonstrates that Fe3+-C12EO4 complexes possess low cytotoxicity, ensuring good biocompatibility. Another advantage of this system is that the DNA complexes can be de-compacted by glutathione in cell without any other agents. This suggests the metal ion-nonionic surfactant complexes as compaction agent can act as the potential delivery tool of DNA in future nonviral gene delivery systems.

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