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Mater."],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Pathological retinal neovascularization (RNV) is a primary etiology of irreversible vision loss in debilitating conditions such as diabetic retinopathy and retinal vein occlusion. While metal-oxide nanomaterials have emerged as potent candidates for anti-angiogenic intervention, their clinical translation remains constrained by persistent biosafety concerns and inherent cytotoxicity. Manganese dioxide nanoparticles (MnO\n                    <jats:sub>2<\/jats:sub>\n                    NPs), distinguished by their robust enzyme-mimetic activity and microenvironment-responsive properties, have demonstrated substantial therapeutic promise in oncology; however, their specific function and underlying mechanisms in RNV remain largely uncharacterized. This study provides a systematic investigation into the anti-angiogenic potential of MnO\n                    <jats:sub>2<\/jats:sub>\n                    NPs and identifies molecular pathways that may underlie their activity, representing a step toward mechanistic proof-of-concept. Our results demonstrate that MnO\n                    <jats:sub>2<\/jats:sub>\n                    NPs possess exceptional biocompatibility both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . These nanoparticles exert a potent, dose-dependent inhibitory effect on the proliferation, migration, and sprouting of human umbilical vein endothelial cells (HUVECs). Moving to\n                    <jats:italic>in vivo<\/jats:italic>\n                    validation, MnO\n                    <jats:sub>2<\/jats:sub>\n                    NPs demonstrate a distinct capacity to modulate physiological retinal vascular development in neonatal mice and, more critically, markedly attenuate pathological neovascularization in an oxygen-induced retinopathy model. Mechanistically, integrated transcriptomic analysis revealed a significant modulation of angiogenesis-related gene clusters, which\u2014along with Western blot validation\u2014confirmed that MnO\n                    <jats:sub>2<\/jats:sub>\n                    NPs exert their effects by targeting the PLK1\/AKT\/FOXO1 signaling axis. In conclusion, MnO\n                    <jats:sub>2<\/jats:sub>\n                    NPs emerge as a compelling and innovative therapeutic candidate for managing vision-threatening ocular vascular disorders. These findings not only offer a targeted pharmacological intervention for retinal diseases but also provide a mechanistic blueprint for the rational design of next-generation multifunctional nanomedicines.\n                  <\/jats:p>","DOI":"10.1088\/1748-605x\/aeaa02","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T22:55:46Z","timestamp":1789772146000},"page":"055014","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Manganese dioxide nanoparticles attenuate pathological retinal angiogenesis by inhibiting the PLK1\/AKT\/FOXO1 signaling axis"],"prefix":"10.1088","volume":"21","author":[{"given":"Min","family":"Zhao","sequence":"first","affiliation":[{"name":"Naval Medical 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