Prolonged Release Period of Nitric Oxide Gas for Treatment of Bacterial Keratitis by Amine-Rich Polymer Decoration of Nanoparticles

Exogeneous nitric oxide (NO) delivery is a promising therapeutic method because NO is a significant cell signaling molecule to control physiological functions. A major challenge for NO delivery is to control release due to the fast diffusion properties of gaseous molecules with low molecular weight. It is important in biomedical applications to mitigate initial burst emissions because higher concentrations of reactive NO cause cytotoxicity and tissue damage. In this study, a nanoparticle system is developed to control spontaneous gas release on the basis of surface-modified silica nanoparticles (Si NPs) by branched polyethylene imine (BPEI). BPEI is not only a scaffold of N-diazeniumdiolates - a type of NO donor - and but also a stabilizer of donors by molecular interactions with nearby amine groups. With the sustained-release manner, BPEI-coated NO-releasing Si NPs (BPEI-NO NPs) have multifunctional properties, including bactericidal efficacies as well as good cell viability for human cells. An improved ocular wound recovery is achieved in the mouse keratitis model. This study demonstrates the great potential of the NO-releasing NP as a multifunctional nanotherapeutic in biomedical applications.