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Cell Squeezing as a Robust, Microfluidic Intracellular Delivery Platform

Cell Squeezing as a Robust, Microfluidic Intracellular Delivery Platform

Published on: November 7, 2013

Engineered carbon dots for mucosal gene delivery.

Samuel Arca¹, Françoise Pons¹, Luc Lebeau¹

¹Laboratoire de Chémo-Biologie Synthétique et Thérapeutique, UMR 7199 CNRS-Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin 67400 Illkirch, France.

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences

|August 1, 2025

Summary

This summary is machine-generated.

Researchers developed mucus-penetrating gene carriers using carbon dots (CDs) to overcome airway mucus barriers for lung gene therapy. Mucolytic-acting CDs significantly improved DNA delivery to lung epithelial cells, offering a promising therapeutic strategy.

Keywords:

Carbon dots Lung gene therapy Mucolytic Mucopenetration Mucus Transfection

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Area of Science:

Biomaterials Science
Gene Therapy
Nanotechnology

Background:

Lung gene therapy faces challenges due to the airway mucus layer, which impedes efficient gene delivery.
Mucociliary clearance rapidly removes therapeutic particles before they reach target epithelial cells.
Developing mucus-penetrating gene carriers is crucial for effective lung gene therapy.

Purpose of the Study:

To engineer novel mucus-penetrating gene carriers based on carbon dots (CDs).
To evaluate strategies for rendering CDs muco-inert, including PEGylation and zwitterionic/mucolytic modifications.
To assess the efficacy of these modified CDs in delivering DNA through mucus to lung cells.

Main Methods:

Synthesized carbon dots (CDs) from citric acid and bPEI600.
Modified CDs with PEG, zwitterionic, or mucolytic species to enhance mucus penetration.
Assessed carrier-mucus interactions using turbidimetry, transport measurements, and rheology.
Evaluated DNA delivery efficiency in cell models, including Calu-3 cells cultured at the air-liquid interface.

Main Results:

CDs modified with mucolytic agents (thiol reservoirs) demonstrated superior mucus penetration and DNA delivery.
PEGylated CDs showed moderate gene transfection, while zwitterion-coated CDs were largely ineffective.
The air-liquid interface Calu-3 cell model effectively discriminated the performance of different CD formulations.

Conclusions:

Carbon dot-based gene carriers, particularly those with mucolytic properties, can effectively penetrate airway mucus.
This approach significantly enhances gene delivery to lung epithelial cells, overcoming a major hurdle in lung gene therapy.
Mucolytic-acting carbon dots represent a promising strategy for developing advanced lung gene delivery systems.