Laser-Triggered Multimodal Cluster Nanobomb for Ultralow-Fluence Vitreolysis and Vitreous Homeostasis Restoration

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Abstract Vitreous floaters affect >80% of people over 60, severely impairing quality of life, yet no safe and effective treatment exists. Nd/YAG laser vitreolysis requires dangerously high fluences, risking retinal injury, and fails to address the underlying pathological cascade. Here, we report a laser-triggered cluster nanobomb (PDN-C) for ultralow-fluence vitreolysis and homeostasis restoration. The nanobomb comprises a magnetic iron-oxide core and targeting-peptide-linked bullets. It actively penetrates the viscous vitreous and anchors to pathological collagen aggregates. Upon pulsed-laser irradiation at a fluence ∼1000-fold lower than clinical Nd/YAG therapy, the core converts the laser into localized microbubble cavitation that ejects the bullets and ablates >87% of collagen mass without retinal phototoxicity. Mechanistically, the ejected bullets achieve a dual-biochemical blockade of the pathogenic ROS-MMP axis: doxycycline inhibits MMP-driven type IV collagen degradation, while the ultrananozyme scavenges ROS, delaying vitreous liquefaction. By coupling precision photomechanical ablation with dynamic microenvironment remodeling, this nanobomb offers a highly effective and safe translational paradigm for vitreous floaters, addressing both the symptoms and the underlying disease pathology.

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