Charge-Converting Nanoemulsions as Promising Retinal Drug and Gene Delivery Systems

Area of Science:

• Biomaterials Science
• Nanotechnology
• Ophthalmology

Background:

• Gene delivery to retinal cells faces challenges with efficiency and targeting.
• Developing responsive nanocarriers is crucial for effective therapeutic delivery.

Purpose of the Study:

• To create novel phosphatase-responsive nanocarriers using polyphosphate-coated, cell-penetrating peptide (CPP)-decorated nanoemulsions (NEs).
• To evaluate these NEs as a gene delivery system for retinal cells.

Main Methods:

• Synthesized amphiphilic PLL-oleylamine (PLOA) conjugates and formed PLOA/TPP NEs.
• Loaded NEs with pGFP plasmid complexed with cationic surfactants.
• Assessed ζ potential conversion, cytotoxicity, cellular uptake, and transfection efficiency in 661W cells.

Main Results:

• Dephosphorylation by alkaline phosphatase (ALP) converted NE ζ potential from negative to positive (-22.4 to +8.5 mV).
• Cellular uptake in 661W cells increased 3-fold compared to controls.
• Achieved low cytotoxicity and high transfection efficacy (∼50% of cells).

Conclusions:

• Polyphosphate-coated, CPP-decorated NEs are triggered by ALP for efficient gene delivery.
• This nanosystem shows promise for treating retinal diseases by targeting photoreceptor-like and other retinal cells.