Targeting nanocomposites with anti-oxidative/inflammatory/angiogenic activities for synergistically alleviating macular degeneration

Treatment of age-related macular degeneration (AMD) is a challenge due to frequent intravitreal injection of drugs, low retention time, risk of infection, need for drugs with multiple therapeutic efficacies, such as anti-inflammatory, anti-oxidant, and anti-angiogenesis. Herein, we demonstrate the synthesis and application of metformin-loaded gold-poly(catechin) core-shell nanoparticles (MF/Au@pCH NPs) as a potential nanocomposite for the treatment of AMD, via sustained drug release to the lesion site. To achieve targeted drug delivery to macula of the AMD eye, we immobilized the complement component protein C3 to form C3-MF/Au@pCH NPs. With this targeted nanocomposite, we aim to utilize the anti-oxidative and anti-inflammatory properties of phenol-rich poly(catechin) and the anti-angiogenic activity of metformin for the synergistic recovery from macular degeneration. The pharmacological efficacy of a single intravitreal dose of C3-MF/Au@pCH NPs is superior to Au@pCH NPs and MF/Au@pCH NPs. In addition, C3-MF/Au@pCH NPs exhibited good in vitro and in vivo biocompatibility. Our study suggests the potential of this multifunctional modality for translation into a clinical intervention for AMD therapy, due to the sustained release of drugs and targeted drug delivery. The findings of this work reveals that Au@pCH NPs could be extended to the treatment of various other diseases with the loading of relative drugs.