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Updated: Jan 28, 2026

Construction of Cyclic Cell-Penetrating Peptides for Enhanced Penetration of Biological Barriers
Published on: September 19, 2022
Population-based analysis of cell-penetrating peptide uptake using a microfluidic droplet trapping array
Nora Safa1, Manibarathi Vaithiyanathan1, Shayan Sombolestani2
1Cain Department of Chemical Engineering, Louisiana State University, Baton Rouge, LA, 70803, USA.
Cell-penetrating peptides (CPPs) show varied uptake in single cells. A microfluidic array revealed peptide concentration and sequence significantly impact cellular uptake efficiency and distribution.
Area of Science:
- Biotechnology
- Cell Biology
- Microfluidics
Background:
- Cell-penetrating peptides (CPPs) are crucial for delivering molecules into cells.
- Understanding single-cell CPP uptake efficiency is limited.
- Heterogeneity in CPP uptake can affect therapeutic outcomes.
Purpose of the Study:
- To characterize CPP uptake efficiency at the single-cell level.
- To compare the permeability of different CPPs in intact cells.
- To investigate factors influencing CPP uptake heterogeneity.
Main Methods:
- Utilized a droplet microfluidic trapping array for single-cell analysis.
- Analyzed fluorescence in a 787-member trapping array with >99% efficiency.
- Employed hierarchical cluster analysis to categorize CPP uptake levels.
Main Results:
- Observed significant heterogeneity in CPP uptake across the cell population.
- Demonstrated that peptide concentration and sequence influence uptake diversity.
- Found CPPs play a role in intracellular peptide distribution homogeneity.
Conclusions:
- Microfluidic analysis provides critical insights into CPP uptake heterogeneity.
- Findings have implications for personalized medicine and drug delivery.
- Understanding uptake variability is essential for biosensor and drug internalization efficacy.
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