Collagenase-modified polydopamine nanoparticles for safe and effective vitreolysis

Anomalous posterior vitreous detachment (aPVD) is involved in the pathogenesis of many vitreoretinal disorders. This condition is currently managed by vitrectomy, a routine but invasive surgery which is especially challenging in patients with firm vitreoretinal adhesions. Since 1998, pharmacological vitreolysis emerged as a potential replacement or adjunct therapy to vitrectomy. Over the years, most attention was focused on enzymes, but their use has been limited mainly due to retinal toxicity. To revive the potential of enzymatic vitreolysis, we aimed to immobilize collagenase on the surface of polydopamine nanoparticles to prevent penetration into the retinal layers. We synthesized stable and functional collagenase-modified nanoparticles and were able to induce vitreous liquefaction and complete PVD ex vivo. Moreover, we demonstrated a substantial reduction in retinal toxicity upon injection in bovine vitreoretinal explants. Subsequent in vivo analysis revealed that retinal morphology and function were preserved, in contrast to free collagenase. Despite the presence of vitreous hemorrhages, which can possibly be avoided by optimization of the experimental set-up, we believe to have given the first step in the right direction towards nanotechnology-based enzymatic vitreolysis and to have opened doors for future research.