Non-covalent complexes between single-stranded oligodeoxynucleotides and poly(ethylene imine)

作者：Smiljanic Danijela; Wesdemiotis Chrys^*

来源：International Journal of Mass Spectrometry, 2011, 304(2-3): 148-153.

DOI：10.1016/j.ijms.2010.06.035

• Polymer
• Oligonucleotide
• Non-covalent complexes
• Solution vs. gas-phase stability
• Gene delivery

Non-covalent complexes between low molecular weight poly(ethylene imine) (PEI 400 and 800) and single-stranded oligodeoxynucleotides (ODNs) were prepared in aqueous solution by combining polymer and ODN in molar ratios ranging from 1:10 to 10:1. Five ODNs were investigated, including d(TTTTT), d(CCCCC), d(AAAAA), d(GGGGG) and d(GCGAT). The compositions, solution stabilities and gas-phase stabilities of the complexes (termed polyplexes) were examined by electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS(2)). Independent of the mixing ratio of the reactants, the polyplex with 1:1 polymer-to-nucleotide stoichiometry. PN, is the dominant product, while the polyplexes PN(2) and P(2)N are observed as byproducts with all ODNs. The relative polyplex ion abundances in the ESI mass spectra reveal the following order of solution stabilities for the major product PN: PEI-d(TTTTT) > PEI-d(GGGGG) approximate to PEI-d(GCGAT) approximate to PEI-d(CCCCC)> PEI-d(AAAAA). The gas-phase stabilities, assessed by MS(2) and collisionally activated dissociation, follow the same order, providing evidence that the polyplex structures in aqueous solution and the more hydrophobic environment of the gas-phase are very similar. PEI 800 leads to more stable polyplexes than PEI 400. PEI-ODN polyplexes have been used in gene delivery. The particularly high binding affinity of d(TTTTT) vs. the other ODNs suggests that sequence-specific delivery systems could be developed by appropriate design of the size and composition of the polymeric delivery vehicle.

• 出版日期2011-7-1