Evaluation of nanorobots for targeted delivery into the retina

Purpose : A major challenge in the treatment of eye diseases in general and retinal diseases in particular, is to deliver drugs to their target sites. Traditional intravitreal injection is based on random, passive diffusion of molecules. In order to specifically address certain structures of the retina, the use of novel particles from biomaterial research promises a more targeted application. The major challenge for such particles is the narrow macromolecular matrix of ocular tissue (including the vitreous body), which acts as a barrier and prevents the penetration of particles. Novel nanorobots from material research - more precisely: nanopropellers - that can be actively controlled through the vitreous body to reach the retina present a chance to reach desired targets in the retina. Methods : The size of the propellers was optimized in the submicrometer diameter, which allows the penetration of the surrounding biopolymer network, in this case the vitreous body. The propulsion takes place through the spiral shape of the magnetic nanopropellers. The fabrication of the nanopropellers consists of two main steps: the preparation of helical nanostructures and a slippery coating. To confirm that the propulsion occurred inside the vitreous, we injected a mixture of nanopropellers and passive silica microparticles into the vitreous of porcine eyes and subjected them to a rotating magnetic field. The porcine eye were obtained from a local abattoir. A standard clinical optical coherence tomography (OCT) instrument for the observation of the nanorobots in a noninvasive and label-free manner was used. To investigate the propulsion of the nanorobots, they were loaded with fluorophores, imaged and analyzed by confocal microscopy and histology. Results : Studies on vitreous bodies in vitro and with ex vivo pig eyes proved that the nanopropellers were driven wirelessly via a rotating magnetic field. Using OCT, the movement of the nanorobots was monitored in real time. The directed propulsion through the vitreous body of the pig's eye is possible over several centimeters. The experiments revealed that the robots can controllably navigate to the retina and histological examinations confirmed that they arrived at the region of interest. Conclusions : The overcoming of adhesion force in the vitreous body and the active navigation of nanopropellers through the dense vitreous body to desired positions in the eye promise new possibilities for targeted therapy. This is a 2020 ARVO Annual Meeting abstract