Mass Spectrometric Detection and Characterization of Metabolites of Gemini Surfactants Used as Gene Delivery Vectors
Date
2020
Authors
Jin, Wei
Purves, Randy
Krol, Ed
Badea, ildiko
El-Aneed, Anas
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Postprint
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Abstract
Gemini surfactants are a class of lipid molecules that have been successfully used in vitro and in vivo as non-viral gene delivery vectors. However, the biological fate of gemini surfactants has not been well investigated. In particular, the metabolism of gemini surfactants after they enter cells as gene delivery vehicles is unknown. In this work, we used a high-resolution quadrupole-Orbitrap mass spectrometry (Q-Exactive®) instrument to detect the metabolites of three model gemini surfactants, namely a) unsubstituted (16-3-16), b) with pyridinium head groups (16(Py)-S-2-S-16(Py)), and c) substituted with a glycyl-lysine di-peptide (16-7N(GK)-16). The metabolites were characterized, and structures proposed, based on accurate masses and characteristic product ions. The metabolism of the three gemini surfactants was very different as 16-3-16 was not metabolized in PAM212 cells, whereas 16(Py)-S-2-S-16(Py) was metabolized primarily via phase I reactions, including oxidation and de-alkylation, producing metabolites that could be linked to its observed high toxicity. The third gemini surfactant 16-7N(GK)-16 was metabolized mainly via phase II reactions, including methylation, acetylation, glucose conjugation, palmityl conjugation, and stearyl conjugation. The metabolism of gemini surfactants provides insight for future directions in the design and development of more effective gemini surfactants with lower toxicity. The reported approach can also be applied to study the metabolism of other structurally related gemini surfactants.
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Keywords
Gemini surfactants, Gene delivery, Metabolites, High resolution mass spectrometry, Efficiency and toxicity, Q-Exactive
Citation
Mass Spectrometric Detection and Characterization of Metabolites of Gemini Surfactants Used as Gene Delivery Vectors. J. Am. Soc. Mass Spectrom. 2020, 31, 2, 366-378. doi.org/10.1021/jasms.9b00004
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Citation
Mass Spectrometric Detection and Characterization of Metabolites of Gemini Surfactants Used as Gene Delivery Vectors. J. Am. Soc. Mass Spectrom. 2020, 31, 2, 366-378. doi.org/10.1021/jasms.9b00004
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DOI
10.1021/jasms.9b00004