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Mass Spectrometric Detection and Characterization of Metabolites of Gemini Surfactants Used as Gene Delivery Vectors

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dc.contributor.authorJin, Wei
dc.contributor.authorPurves, Randy
dc.contributor.authorKrol, Ed
dc.contributor.authorBadea, ildiko
dc.contributor.authorEl-Aneed, Anas
dc.date.accessioned2023-11-16T18:12:27Z
dc.date.available2023-11-16T18:12:27Z
dc.date.issued2020
dc.description.abstractGemini 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.en_US
dc.description.sponsorshipNSERCen_US
dc.description.versionPeer Revieweden_US
dc.identifier.citationMass 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.9b00004en_US
dc.identifier.doi10.1021/jasms.9b00004
dc.identifier.urihttps://hdl.handle.net/10388/15251
dc.language.isoenen_US
dc.rightsAttribution-NonCommercial-ShareAlike 2.5 Canada*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/2.5/ca/*
dc.subjectGemini surfactantsen_US
dc.subjectGene deliveryen_US
dc.subjectMetabolitesen_US
dc.subjectHigh resolution mass spectrometryen_US
dc.subjectEfficiency and toxicityen_US
dc.subjectQ-Exactiveen_US
dc.titleMass Spectrometric Detection and Characterization of Metabolites of Gemini Surfactants Used as Gene Delivery Vectorsen_US
dc.typePostprinten_US

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