Laser-Triggered Liposomal Nanoparticles Combining Antiangiogenic and Photodynamic Therapy for Ocular Neovascularization

Ophthalmic drug delivery faces significant challenges, including the poor solubility of hydrophobic agents, as well as limited permeability and rapid clearance caused by the eye's intricate anatomical and physiological barriers. In this study, laser-triggered core-shell structural liposomal nanoparticles (Lips-NPs@Axi/Vp) were designed for precise drug delivery and offered a potential treatment strategy for ocular neovascularization by incorporating both antiangiogenic and photodynamic therapy. Laser-triggered in vitro release and intensive reactive oxygen species (ROS) production of Lips-NPs@Axi/Vp were noted. Furthermore, Lips-NPs@Axi/Vp markedly suppressed cell proliferation and tube formation of EA.hy.926 cells while revealing minimal toxicity toward human corneal epithelial cells (HCECs). Besides, the liposomal nanoparticle system exhibited extended corneal residence time exceeding 4 h, significantly facilitating drug bioavailability. Through their combined anti-inflammatory, photodynamic, and anti-VEGF effects, Lips-NPs@Axi/Vp successfully maintained corneal clarity and prevented alkali-burn-induced corneal neovascularization in animal models. The findings suggested that this multifunctional nanotherapeutic system represented a potential breakthrough for treating neovascular ocular diseases and offered significant advantages over traditional eye medications through its extended duration of action and improved therapeutic response.