Humanized Biomimetic Nanovesicles for Neuron Targeting.

Area of Science:

• Biomedical Engineering
• Neuroscience
• Materials Science

Background:

• Nanovesicles (NVs) are promising for targeted drug delivery.
• Engineering NVs with cell membrane proteins can improve biocompatibility and function.
• Biomimetic NVs using human neural cell proteins have not been explored for neurological applications.

Purpose of the Study:

• To develop and validate scalable production of neuron-targeting NVs using human neural cell membrane proteins.
• To assess the physicochemical properties, neuronal association, and uptake of these biomimetic NVs.
• To evaluate the potential of these NVs for neuroregeneration therapies.

Main Methods:

• Optimized scalable production of two NV types with distinct lipid formulations.
• Integrated endogenous and engineered membrane proteins from human pluripotent stem-cell-derived neurons.
• Assessed NV physicochemical properties, neuronal association, and uptake in 3D neural spheres and rodent cranial nerves.

Main Results:

• Successful transfer of neural membrane proteins to NVs without altering properties.
• NVs with neuron-derived proteins showed enhanced neuronal association and uptake compared to bare NVs.
• NV treatment did not affect the viability of 3D neural sphere cultures, validating organoid platforms.
• Confirmed cellular uptake of biomimetic NVs in rodent cranial nerve neurons.

Conclusions:

• Customizable, biomimetic NVs can be produced scalably using human neural cell membrane proteins.
• These NVs demonstrate improved targeting and uptake by neurons.
• The developed NVs hold potential as next-generation theranostics for promoting neuroregeneration.