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Related Experiment Video

Updated: May 28, 2026

In Vivo Imaging of Transduction Efficiencies of Cardiac Targeting Peptide

In Vivo Imaging of Transduction Efficiencies of Cardiac Targeting Peptide

Published on: June 11, 2020

Direct translocation as major cellular uptake for CADY self-assembling peptide-based nanoparticles.

Anna Rydström¹, Sébastien Deshayes, Karidia Konate

¹Centre de Recherches de Biochimie Macromoléculaire, CRBM-CNRS, UMR-5237, UM1-UM2, Department of Molecular Biophysics and Therapeutics, University of Montpellier, Montpellier, France.

|October 15, 2011

Summary

Cell penetrating peptides like CADY deliver siRNA effectively by directly crossing cell membranes. This mechanism bypasses endosomes, ensuring siRNA reaches the cytoplasm without harming cells.

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In Vivo Imaging of Transduction Efficiencies of Cardiac Targeting Peptide

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Published on: June 11, 2020

Delivery of Proteins, Peptides or Cell-impermeable Small Molecules into Live Cells by Incubation with the Endosomolytic Reagent dfTAT

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Construction of Cyclic Cell-Penetrating Peptides for Enhanced Penetration of Biological Barriers

Construction of Cyclic Cell-Penetrating Peptides for Enhanced Penetration of Biological Barriers

Published on: September 19, 2022

Area of Science:

Biochemistry
Cell Biology
Nanotechnology

Background:

Cell penetrating peptides (CPPs) offer a promising strategy for in vivo siRNA delivery.
Limitations in current siRNA delivery necessitate novel approaches for efficient cellular uptake.

Purpose of the Study:

To elucidate the cellular uptake mechanism of CADY:siRNA complexes.
To investigate the role of endosomal pathways versus direct translocation in CADY:siRNA cellular entry.

Main Methods:

Biochemical assays
Confocal microscopy
Electron microscopy
Endosomal pathway inhibition studies

Main Results:

CADY:siRNA complexes primarily enter cells via direct membrane translocation, not endocytosis.
Complexes showed no colocalization with endosomal markers and remained active when endocytosis was inhibited.
Cellular entry was independent of electrostatic interactions with heparan sulfates and membrane potential.
CADY:siRNA induced transient membrane permeabilization, rapidly restored by membrane fluidity.

Conclusions:

Direct translocation is the predominant mechanism for CADY:siRNA cellular uptake.
CADY's interaction with phospholipids drives membrane perturbation and cytoplasmic delivery.
The process maintains cell integrity and viability.