Uptake of Polyelectrolyte Functionalized Upconversion Nanoparticles by Tau-Aggregated Neuron Cells

Area of Science:

• Neuroscience
• Biomaterials Science
• Nanotechnology

Background:

• Tauopathy, characterized by tau protein aggregation, is linked to neurodegenerative diseases.
• The precise mechanisms of tau aggregate metastasis between neurons remain incompletely understood.
• Concerns exist regarding the long-term cellular impact of non-biodegradable drug delivery systems.

Purpose of the Study:

• To investigate the uptake and intracellular delivery mechanisms of nano-sized carriers in tau-aggregated neurons.
• To evaluate the influence of nanoparticle size on cellular interactions within the context of tauopathy.
• To assess the pharmacokinetic implications for drug delivery systems targeting neurodegenerative diseases.

Main Methods:

• Utilized polyelectrolyte-functionalized upconversion nanoparticles (UCNPs) with a diameter of approximately 100 nm.
• Induced tau aggregation in healthy neuron cells using forskolin and okadaic acid.
• Employed near-infrared light irradiation for bioimaging to track nanoparticle behavior.

Main Results:

• Tau-aggregated neuron cells exhibited similar uptake efficiency for ~100 nm UCNPs compared to normal neurons.
• Intracellular transport and exocytosis of UCNPs were significantly impacted in tau-aggregated cells.
• A majority of the UCNPs accumulated around lysosomes in tau-aggregated neurons.

Conclusions:

• Nanoparticle size critically influences cellular transport and exocytosis in tau-aggregated neurons.
• The findings highlight the need to consider carrier size in pharmacokinetic studies for tauopathy drug delivery.
• Understanding these interactions is crucial for designing effective and safe nanomedicines for neurodegenerative diseases.