Selective Endocytic Uptake of Targeted Liposomes Occurs within a Narrow Range of Liposome Diameters

Area of Science:

• Cell biology
• Biophysics
• Nanotechnology

Background:

• Cell surface receptors mediate essential cellular functions like signaling and nutrient uptake.
• Receptor recycling via endocytosis is crucial for cellular dynamics.
• Targeted drug delivery systems utilize ligands on carrier particles to bind cell surface receptors, often entering via clathrin-mediated endocytosis.

Purpose of the Study:

• To elucidate the detailed mechanisms of particle uptake by observing individual endocytic events.
• To investigate the influence of liposome characteristics, specifically size and ligand density, on cellular internalization.
• To identify limitations in targeted drug delivery systems and inform the design of more effective carriers.

Main Methods:

• Live-cell imaging was employed to track individual liposome-cell interactions.
• The uptake of liposomes interacting with clathrin-coated structures was observed at the single-event level.
• Liposome size and surface ligand density were systematically varied and their impact on internalization probability assessed.

Main Results:

• Liposome size was identified as the primary determinant of cellular uptake probability, surpassing ligand density.
• Targeting efficacy was most pronounced for liposomes of intermediate diameters.
• Very small liposomes were consistently internalized, while very large liposomes were excluded, irrespective of targeting.

Conclusions:

• Cellular uptake of targeted liposomes is significantly influenced by particle size, presenting a critical factor for drug delivery system design.
• The effectiveness of ligand-mediated targeting is size-dependent, with limitations observed for both small and large liposomes.
• These findings provide a mechanistic understanding to optimize liposome-based drug carriers for enhanced therapeutic efficacy.