The utilization of pathogen-like cellular trafficking by single chain block copolymer

Area of Science:

• Biomaterials Science
• Cell Biology
• Neuroscience

Background:

• Amphiphilic triblock copolymers like Pluronic P85 are used in drug delivery.
• Brain microvessel endothelial cells and neurons are challenging to deliver substances into.

Purpose of the Study:

• To investigate the cellular uptake and trafficking mechanisms of Pluronic P85 in brain endothelial cells and neurons.
• To explore alternative cellular entry pathways for synthetic polymers.

Main Methods:

• Utilized Pluronic P85 (poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide)) in brain microvessel endothelial cells and primary neurons.
• Investigated cellular entry sites including caveolae and clathrin-dependent pathways.
• Tracked copolymer trafficking to intracellular compartments like the endoplasmic reticulum and mitochondria.

Main Results:

• Pluronic P85 enters poorly penetrable brain microvessel endothelial cells and primary neurons.
• Caveolae are a primary entry site, but caveolae- and clathrin-independent routes are also utilized.
• The copolymer bypasses early endosomes/lysosomes, traffics to the endoplasmic reticulum, and ultimately reaches mitochondria.
• In neurons, Pluronic P85 accumulates in the cell body and undergoes anterograde trafficking.

Conclusions:

• Pluronic P85 employs sophisticated cellular trafficking, mimicking pathogen entry.
• The findings enable the development of novel delivery systems for targeting intracellular compartments in previously impenetrable cells.