Intrinsic and Universal Therapy of Both Dry and Wet Age‐Related Macular Degeneration via Non‐Invasive Administration of Biomimetic Mesoporous Polydopamine Nanoparticles

ABSTRACT Age‐related macular degeneration (AMD), a leading cause of blindness in developed countries, is classified into dry (dAMD) and wet (wAMD) forms. Many patients progress from dry to wet AMD, underscoring the need for universal treatments and minimally invasive routes. Inspired by natural melanin's antioxidant properties and dopamine's anti‐angiogenic effects, melanin‐biomimetic polydopamine (PDA) was explored for the non‐invasive treatment of both types of AMD. The influence of the structural characteristics of PDA on its therapeutic efficacy was further investigated. Herein, using D‐α‐tocopherol polyethylene glycol succinate (TPGS) as a stabilizer, conventional polydopamine nanoparticles (TPDA) and mesoporous polydopamine nanoparticles (TMPDA) were developed. Compared with TPDA, TMPDA demonstrated stronger antioxidant capacity and anti‐angiogenic activity in vitro. In rabbit eyes, topically administered TMPDA exhibited enhanced intraocular retention and retinal distribution. In pharmacodynamic models of dAMD and wAMD, TMPDA eye drops achieved therapeutic effects comparable to those of intravitreally injected TPDA and TMPDA, with an inhibition rate exceeding 60% after 14 days of treatment. This study is the first to demonstrate the broad‐spectrum efficacy of surface‐roughened mesoporous TMPDA nanoparticles for treating both wAMD and dAMD via topical eye drop administration, presenting a promising non‐invasive alternative to intravitreal injections.