Magnetoelectric Extracellular Vesicle Latency-Targeting (MELT) Nanotherapeutic for the Block-Lock-and-Kill HIV...

Area of Science:

• Neuroscience
• Nanotechnology
• Virology

Background:

• Human immunodeficiency virus (HIV) establishes latent infections in microglia, a key cellular reservoir.
• HC69 cells, a microglial model, express GFP under HIV promoter control (LTR) to indicate latency.
• GFP expression is low (GFP^Lo) at rest and high (GFP^Hi) upon activation.

Purpose of the Study:

• To evaluate the efficacy of a two-step nanotherapeutic, MELT, for targeting HIV latency in microglia.
• To assess the ability of MELT to reduce HIV LTR transcriptional reactivation.

Main Methods:

• MELT involves two steps: ZL0580-loaded extracellular vesicles (EVs) and monomethyl auristatin E (MMAE)-conjugated magnetoelectric nanoparticles (MENPs).
• ZL0580-EVs inhibited LTR reactivation by 50% with reduced toxicity.
• MMAE-MENPs were internalized by HC69 cells, with higher uptake in GFP^Lo cells.

Main Results:

• MELT demonstrated the ability to cross the blood-brain barrier (BBB) in a Transwell model.
• 20% of MELT crossed the BBB and was internalized by HC69 cells.
• MELT reduced LTR reactivation by 10% in the tested model.

Conclusions:

• The study demonstrates the potential of MELT as a nanotherapeutic strategy for targeting HIV latency in microglia.
• MELT shows promise in reducing HIV LTR reactivation, a key indicator of viral latency.