Noninvasive Framework Nucleic Acid Eye Drops for Retinal Administration

Intravitreal injection is widely employed for the treatment of retinal diseases. However, it suffers from various drawbacks, including ocular trauma, risk of infection, and poor patient compliance due to frequent administrations. Due to the presence of barriers such as the cornea, it has been a challenge to develop efficient noninvasive ophthalmic eye drops that can reach the retina. Framework nucleic acids (FNAs), known for their excellent biocompatibility and precise, controllable shape and size, have been extensively utilized in drug delivery application. Here, we report the development of size- and shape-resolved fluorescent DNA frameworks for noninvasive retinal administration. Results show that tetrahedral DNA nanostructures (TDNs) with an edge length of 20 bp can reach the retina within 6 h with the highest efficiency. Moreover, this delivery method exhibits excellent biocompatibility. Our findings provide an approach for the development of localized treatment strategies for retinal diseases using FNA-based nanocarriers.