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Self-Assembly of DNA–Minocycline Complexes by Metal Ions with Controlled Drug Release

Zhang, Ting, Nong, Jia, Alzahrani, Nouf, Wang, Zhicheng, Oh, Sung Won, Meier, Tristan, Yang, Dong Gyu, Ke, Yonggang, Zhong, Yinghui, Fu, Jinglin
ACS applied materials & interfaces 2019 v.11 no.33 pp. 29512-29521
agarose, bioactive properties, calcium, cations, divalent metals, drug delivery systems, drugs, gels, macrophages, magnesium, metal ions, nitric oxide, nitrogen, phosphates, single-stranded DNA, tetracycline, zwitterions
Here we reported a study of metal ions-assisted assembly of DNA–minocycline (MC) complexes and their potential application for controlling MC release. In the presence of divalent cations of magnesium or calcium ions (M²⁺), MC, a zwitterionic tetracycline analogue, was found to bind to phosphate groups of nucleic acids via an electrostatic bridge of phosphate (DNA)-M²⁺-MC. We investigated multiple parameters for affecting the formation of DNA-Mg²⁺-MC complex, including metal ion concentrations, base composition, DNA length, and single- versus double-stranded DNA. For different nitrogen bases, single-stranded poly(A)₂₀ and poly(T)₂₀ showed a higher MC entrapment efficiency of DNA-Mg²⁺-MC complex than poly(C)₂₀ and poly(G)₂₀. Single-stranded DNA was also found to form a more stable DNA-Mg²⁺-MC complex than double-stranded DNA. Between different divalent metal ions, we observed that the formation of DNA-Ca²⁺-MC complex was more stable and efficient than the formation of DNA-Mg²⁺-MC complex. Toward drug release, we used agarose gel to encapsulate DNA-Mg²⁺-MC complexes and monitored MC release. Some DNA-Mg²⁺-MC complexes could prolong MC release from agarose gel to more than 10 days as compared with the quick release of free MC from agarose gel in less than 1 day. The released MC from DNA-Mg²⁺-MC complexes retained the anti-inflammatory bioactivity to inhibit nitric oxide production from pro-inflammatory macrophages. The reported study of metal ion-assisted DNA-MC assembly not only increased our understanding of biochemical interactions between tetracycline molecules and nucleic acids but also contributed to the development of a highly tunable drug delivery system to mediate MC release for clinical applications.