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In this study, the potent iron\u2010binding nanoscale Prussian blue analogue KCa[Fe<jats:sup>III<\/jats:sup>(CN)<jats:sub>6<\/jats:sub>] (CaPB) with high biocompatibility is designed to inhibit RPE death and subsequently photoreceptor cell degeneration. In mice, CaPB effectively prevents RPE degeneration and ultimately fulfills superior therapeutic outcomes upon a single intravitreal injection: significant rescue of retinal structures and visual function. Through high\u2010throughput RNA sequencing and sophisticated biochemistry evaluations, the findings initially unveil that CaPB nanoparticles protect against RPE degradation by inhibiting ferroptotic cell fate. Together with the facile, large\u2010scale preparations and in vivo biosafety, it is believed that the synthesized CaPB therapeutic nanoparticles are promising for future clinical treatment of diverse retinal diseases involving pathological iron\u2010dependent ferroptosis, including AMD.<\/jats:p>","DOI":"10.1002\/smtd.202100848","type":"journal-article","created":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T05:22:54Z","timestamp":1636608174000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Nanoprotection Against Retinal Pigment Epithelium Degeneration via Ferroptosis Inhibition"],"prefix":"10.1002","volume":"5","author":[{"given":"Zhimin","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 200011 P. R. 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