Melanin-like Nanoparticles as an Alternative to Natural Melanin in Retinal Pigment Epithelium Cells and Their Therapeutic Effects against Age-Related Macular Degeneration

Abstract

Melanin is a natural pigment that is widely distributed in many parts of the human body, such as the skin and retinal pigment epithelium (RPE) in eyes. In contrast to skin melanin, which is being constantly synthesized by the epidermal melanocytes, melanin in the RPE does not regenerate. Melanin is known to function as a potential radical scavenger and photoprotective agent. However, the protective effects of melanin against oxidative stress decline with increasing age. This phenomenon has been correlated with the pathogenesis of age-related macular degeneration (AMD). To increase the potential antioxidant and photoprotective characteristics of melanin, we designed a therapeutic strategy for replenishment of melanin using PEGyl­ated synthetic melanin-like nanoparticles (MNPs) in the RPE for the treatment of AMD. We performed experiments using AMD-like cellular and mouse models and demonstrated that MNPs are biocompatible and selectively target reactive oxygen species (ROS) with powerful antioxidant properties. MNPs can traffic and accumulate in the RPE and are exclusively located in cytosol, but not the nucleus and mitochondria of the cells, for at least 3 months after a single-dose intra­vitreal injection. Our findings demonstrate that MNPs are able to substitute for natural melanin in the RPE and suggest the potential efficacy of MNPs as a natural radical scavenger against oxidative stress in ROS-related diseases, such as AMD.

Mesoporous Cerium Oxide Nanoparticles with High Scavenging Properties of Reactive Oxygen Species for Treating Age‐Related Macular Degeneration

“…[50] PEGylated, dopamine-derived synthetic melanin-like nanoparticles demonstrated good biocompatibility and robust antioxidant capability, effectively mitigating pathological structural damage in a laser-induced CNV mouse model and in a light-damaged, NRF2-deficient retinal degeneration mouse model, respectively. [51] Furthermore, the integration of CeNPs into melanin-like nanoparticles endowed multiantioxidative activity against reactive oxygen and nitrogen species, while reducing the level of proinflammatory cytokines, ultimately alleviating AMD-like pathology in a laser-induced CNV mouse model. [52] Solid lipid nanoparticles coloaded with microRNA-150, which regulates pathological angiogenesis, and quercetin as an antioxidant and anti-inflammatory drug, demonstrated a promising suppressive effect on the generation and progression of CNV in vivo.…”

Revolutionizing eye care: the game-changing applications of nano-antioxidants in ophthalmology

“…Kwon et al designed a therapeutic strategy for the replenishment of melanin using PEGylated synthetic melanin-like NPs (MNPs) in the RPE for the treatment of AMD. 97 They synthesized MNPs with thiol-terminated methoxy polyethylene glycol (mPEG-SH) attached to the NPs to improve the stability. MNPs could target mitochondria-specific ROS and had excellent ROS scavenging ability.…”

Revitalizing Ancient Mitochondria with Nano‐Strategies: Mitochondria‐Remedying Nanodrugs Concentrate on Disease Control

“…Persistent and unregulated inflammation is always found in numerous human diseases with obvious mitochondrial damage, which is not limited to autoimmune disease [108] but also includes neurological, [109] cardiovascular, [110] renal, and hepatic disease. [111,112] The inflammation will as a bona fide disease driver or an accomplice in disease deterioration. Dating back a long time ago, mitochondria were believed as evolutionary remnants of bacteria.…”

“…Antioxidative nanodrugs, such as MitoQ, [ 341 ] melanin, [ 112 ] quercetin nanomedicine, [ 340 ] and glycol chitosan cerium oxide NPs (GCCNP), [ 342 ] have held promising results in combating oxidative stress to protect mitochondria during ocular disease treatment. These antioxidant nanodrugs can directly combat severe retinal damage after penetrating the retina.…”