ArticleThe AAPS journal2019
Cellular Uptake and Distribution of Gemini Surfactant Nanoparticles Used as Gene Delivery Agents.
Article in The AAPS journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Surfactant-Enabled Nanocarriers in Breast Cancer Therapy: Targeted Delivery and Multidrug Resistance Reversal.Pharmaceutics · 2025Review
- Cationic Serine-Based Gemini Surfactant:Monoolein Aggregates as Viable and Efficacious Agents for DNA Complexation and Compaction: A Cytotoxicity and Physicochemical Assessment.Journal of functional biomaterials · 2024Article
- The Interaction of a Gemini Surfactant with a DNA Quadruplex.ACS omega · 2024Article
- Nanoscale Structure of Lipid-Gemini Surfactant Mixed Monolayers Resolved with AFM and KPFM Microscopy.Nanomaterials (Basel, Switzerland) · 2024Article
- HJournal of nanobiotechnology · 2022Article
- Non-viral Vectors in Gene Therapy: Recent Development, Challenges, and Prospects.The AAPS journal · 2021Review
- Application of advances in endocytosis and membrane trafficking to drug delivery.Advanced drug delivery reviews · 2020Review
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gemini 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. Graphical Abstract.
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