DNA Origami Nanoparticles with Oligolysine Coating Show Promise for Retinal Cell Uptake
Researchers found that coating DNA origami nanoparticles (DONs) with a PEG5K-K10 block-copolymer significantly enhanced their uptake into Y-79 retinoblastoma cells while preserving their ability to diffuse through vitreous humor in ex vivo porcine eyes. The study also tested a PL3 targeting peptide in combination with the coating, but found it provided no additional benefit. These findings advance the development of DNA-based nanocarriers for ocular drug delivery, particularly for hard-to-treat eye diseases like retinoblastoma.
A study posted to bioRxiv investigated how surface coatings affect the cellular uptake and ocular mobility of DNA origami nanoparticles (DONs), which are programmable nanostructures with potential as drug delivery vehicles for eye diseases. The researchers coated 24-helix bundle DONs with PEG5K-K10, a cationic PEG-oligolysine block-copolymer, and tested uptake in Y-79 retinoblastoma cells. They found that uptake only occurred once a threshold amount of PEG5K-K10 coating was applied, and that longer exposure times or higher polymer concentrations further improved cell association. A dual strategy combining PEG5K-K10 with PL3 targeting peptides did not yield additional uptake benefits over the coating alone. Importantly, while free PEG5K-K10 reduced cell viability at higher concentrations (IC50 of 36.8 µM), DONs coated with the polymer were well-tolerated by cells. Single-particle tracking in ex vivo porcine eyes showed that coated DONs retained vitreous mobility comparable to uncoated particles, with only a slight reduction at higher coating amounts. The authors conclude that PEG5K-K10 coating represents a promising strategy for improving ocular drug delivery without compromising nanoparticle diffusion through the eye.
What's missing
The study is a preprint and has not yet undergone peer review. All cellular uptake experiments were conducted in a single retinoblastoma cell line (Y-79), limiting generalizability to other ocular cell types or in vivo conditions. The ex vivo porcine eye model may not fully replicate human vitreous properties. Long-term biocompatibility, in vivo efficacy, and drug-loading capacity of the coated DONs were not assessed. The mechanism by which PEG5K-K10 promotes cellular internalization was not fully elucidated.
What different sources said
- bioRxivCenter
DNA origami uptake in Y-79 retinoblastoma cells driven by oligolysine coating
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