{Reference Type}: Journal Article
{Title}: C176-loaded and phosphatidylserine-modified nanoparticles treat retinal neovascularization by promoting M2 macrophage polarization.
{Author}: Shao A;Jin L;Ge Y;Ye Z;Xu M;Zhou Y;Li Y;Wang L;Xu P;Jin K;Mao Z;Ye J;
{Journal}: Bioact Mater
{Volume}: 39
{Issue}: 0
{Year}: 2024 Sep
{Factor}: 16.874
{DOI}: 10.1016/j.bioactmat.2024.05.038
{Abstract}: Retinal neovascularization (RNV), a typical pathological manifestation involved in most neovascular diseases, causes retinal detachment, vision loss, and ultimately irreversible blindness. Repeated intravitreal injections of anti-VEGF drugs were developed against RNV, with limitations of incomplete responses and adverse effects. Therefore, a new treatment with a better curative effect and more prolonged dosage is demanding. Here, we induced macrophage polarization to anti-inflammatory M2 phenotype by inhibiting cGAS-STING signaling with an antagonist C176, appreciating the role of cGAS-STING signaling in the retina in pro-inflammatory M1 polarization. C176-loaded and phosphatidylserine-modified dendritic mesoporous silica nanoparticles were constructed and examined by a single intravitreal injection. The biosafe nanoparticles were phagocytosed by retinal macrophages through a phosphatidylserine-mediated "eat me" signal, which persistently release C176 to suppress STING signaling and thereby promote macrophage M2 polarization specifically. A single dosage can effectively alleviate pathological angiogenesis phenotypes in murine oxygen-induced retinopathy models. In conclusion, these C176-loaded nanoparticles with enhanced cell uptake and long-lasting STING inhibition effects might serve as a promising way for treating RNV.