Investigating Internalization of Reporter-Protein-Functionalized Polyhedrin Particles by Brain Immune Cells

Area of Science:

• Neuroscience
• Biomaterials Science
• Drug Delivery

Background:

• Sustained central nervous system (CNS) drug delivery is crucial for treating neurological disorders.
• Polyhedrin Delivery System (PODS) are protein-based nanoparticles for therapeutic delivery.
• Understanding microglia interaction with biomaterials is vital for CNS applications.

Purpose of the Study:

• To evaluate the interaction of PODS with primary mouse cortical microglia.
• To assess the acute toxicity and cellular response of microglia to PODS.
• To determine the internalization and localization of PODS within microglia.

Main Methods:

• Primary mouse cortical microglia were cultured with GFP-functionalized PODS for 24 hours.
• Cell counts, morphology, and Iba1 expression were analyzed to assess microglial activation and toxicity.
• Microscopy was used to observe PODS internalization and localization within microglia.

Main Results:

• PODS did not alter microglia cell counts, morphology, or Iba1 expression, indicating no acute toxicity or activation.
• Microglia internalized PODS, with both cytosolic and perinuclear localization observed.
• 20-40% of microglia showed PODS uptake, with significant extracellular PODS remaining after 24 hours.

Conclusions:

• PODS exhibit low acute toxicity to microglia, a key neural immune cell.
• Microglia internalize PODS, but a portion remains extracellular, suggesting potential for sustained drug release.
• PODS are a promising platform for CNS drug delivery, warranting further investigation for neurological applications.