DNA Origami Nanoparticles with Oligolysine Coating Show Promise for Retinal Cell Uptake
Researchers found that coating DNA origami nanoparticles with PEG5K-K10, a cationic polymer, significantly improves their uptake into retinoblastoma cells while maintaining safety and mobility in the eye. The coating was essential for cell internalization and did not impair the particles' ability to diffuse through the vitreous humor. These findings suggest DNA origami nanoparticles could be viable carriers for delivering therapeutic agents to treat eye diseases.
A study published on bioRxiv investigated how to improve the cellular uptake of DNA origami nanoparticles (DONs)—engineered DNA structures with potential applications in ocular drug delivery. The researchers coated 24-helix bundle DNA origami structures with PEG5K-K10, a polymer that adds positive charge to overcome the particles' natural negative charge and poor cell penetration. Uptake experiments in Y-79 retinoblastoma cells demonstrated that the polymer coating was critical for internalization, with greater coating amounts and longer exposure times increasing cell association. While the addition of a targeting peptide (PL3) provided no additional benefit, the coated nanoparticles were well-tolerated by cells even at concentrations where free polymer alone reduced viability. Single-particle tracking in porcine eye tissue showed that the coating did not significantly impair the nanoparticles' ability to move through the vitreous, suggesting they could maintain therapeutic efficacy after delivery.
Limitations & open questions
The study does not discuss the specific mechanisms by which PEG5K-K10 facilitates cell uptake (e.g., endocytosis pathways), the long-term stability of coated particles in physiological conditions, or comparative efficacy data against existing ocular drug delivery systems. Additionally, the authors note that the targeting peptide PL3 showed no benefit, but do not provide mechanistic explanation for this negative result.
What different sources said
- bioRxivCenter
DNA origami uptake in Y-79 retinoblastoma cells driven by oligolysine coating
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