Precision intracellular delivery based on optofluidic polymersome rupture

Area of Science:

• Biotechnology
• Cell Biology
• Materials Science

Background:

• Intracellular delivery of molecules is crucial for various biological applications.
• Existing methods like liposomes and nanoparticles face limitations in speed and efficiency.
• Polymersomes offer potential for controlled cargo release but require optimization for rapid intracellular delivery.

Purpose of the Study:

• To develop a novel optical method for rapid intracellular delivery of molecules encapsulated in polymersomes.
• To investigate the mechanism of light-induced polymersome rupture and payload release.
• To demonstrate the efficiency of this method in delivering payloads into phagocytic cells and facilitating endosomal escape.

Main Methods:

• Utilized oxidation-sensitive polymersomes incorporating the photosensitizer ethyl eosin.
• Applied optical excitation to trigger oxidative changes in the polymersome membrane, inducing rupture.
• Studied the intracellular delivery and payload distribution in RAW macrophages and dendritic cells.
• Quantified delivery kinetics and endosomal escape using cellular assays.

Main Results:

• Optical activation rapidly induced polymersome rupture and payload release within seconds.
• Delivered payloads rapidly distributed throughout the cell cytosol within milliseconds.
• Achieved intracellular delivery and endosomal escape simultaneously upon illumination.
• Demonstrated a 100-fold increase in delivery speed compared to conventional carrier-mediated methods.
• Successfully delivered a peptide antigen into dendritic cells and measured MHC I presentation kinetics.

Conclusions:

• The presented optofluidic method provides a highly efficient and rapid approach for intracellular molecule delivery.
• This technique enables simultaneous payload delivery and endosomal escape, overcoming key biological barriers.
• The method has significant potential for applications in quantitative cell biology, drug delivery, and studying intercellular processes.