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Cellular Uptake and Distribution of Gemini Surfactant Nanoparticles Used as Gene Delivery Agents

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dc.contributor.authorJin, Wei
dc.contributor.authorAl-Dulaymi, Mays
dc.contributor.authorBadea, Ildiko
dc.contributor.authorLeary, Scot
dc.contributor.authorRehman, Jeveria
dc.contributor.authorEl-Aneed, Anas
dc.date.accessioned2023-06-16T16:37:38Z
dc.date.available2023-06-16T16:37:38Z
dc.date.issued2019-08-06
dc.description.abstractGemini surfactants are promising molecules utilized as non-viral gene delivery vectors. However, little is known about their cellular uptake and distribution after they release their therapeutic cargo. Therefore, we quantitatively evaluated the cellular uptake and distribution of three gemini surfactants: unsubstituted (16-3-16), with pyridinium head groups (16(Py)-S-2-S-16(Py)) and substituted with a glycyl-lysine di-peptide (16-7N(GK)-16). We also assessed the relationship between cellular uptake and distribution of each gemini surfactant and its overall efficiency and toxicity. Epidermal keratinocytes PAM 212 were treated with gemini surfactant nanoparticles formulated with plasmid DNA and harvested at various time points to collect the enriched nuclear, mitochondrial, plasma membrane, and cytosolic fractions. Gemini surfactants were then extracted from each subcellular fraction and quantified using a validated flow injection analysis-tandem mass spectrometry (FIA-MS/MS) method. Mass spectrometry is superior to the use of fluorescent tags that alter the physicochemical properties and pharmacokinetics of the nanoparticles and can be cleaved from the gemini surfactant molecules within biological systems. Overall, a significantly higher cellular uptake was observed for 16-7N(GK)-16 (17.0%) compared with 16-3-6 (3.6%) and 16(Py)-S-2-S-16(Py) (1.4%), which explained the relatively higher transfection efficiency of 16-7N(GK)-16. Gemini surfactants 16-3-16 and 16(Py)-S-2-S-16(Py) displayed similar subcellular distribution patterns, with major accumulation in the nucleus, followed by the mitochondrion, cytosol, and plasma membrane. In contrast, 16-7N(GK)-16 was relatively evenly distributed across all four subcellular fractions. However, accumulation within the nucleus after 5 h of treatment was the highest for 16(Py)-S-2-S-16(Py) (50.3%), followed by 16-3-16 (41.8%) and then 16-7N(GK)-16 (33.4%), possibly leading to its relatively higher toxicity.en_US
dc.description.sponsorshipNSERC and CFIen_US
dc.description.versionPeer Revieweden_US
dc.identifier.citationJin, W., Al-Dulaymi, M., Badea, I. et al. Cellular Uptake and Distribution of Gemini Surfactant Nanoparticles Used as Gene Delivery Agents. AAPS J 21, 98 (2019). https://doi.org/10.1208/s12248-019-0367-1en_US
dc.identifier.doi10.1208/s12248-019-0367-1
dc.identifier.urihttps://hdl.handle.net/10388/14725
dc.language.isoen_USen_US
dc.publisherSpringerLinken_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.subjectsubcellular distributionen_US
dc.subjectFIA-MS/MSen_US
dc.subjecttoxicityen_US
dc.subjecttransfectionen_US
dc.titleCellular Uptake and Distribution of Gemini Surfactant Nanoparticles Used as Gene Delivery Agentsen_US
dc.typePostprinten_US

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