2. Academic Validation
  3. ROS-responsive drug delivery system with enhanced anti-angiogenic and anti-inflammatory properties for neovascular age-related macular degeneration therapy

ROS-responsive drug delivery system with enhanced anti-angiogenic and anti-inflammatory properties for neovascular age-related macular degeneration therapy

  • Mater Today Bio. 2025 Apr 10:32:101757. doi: 10.1016/j.mtbio.2025.101757.
Jiayi Zuo 1 2,  Yining Pan 1 2,  Yuanli Wang 1 2,  Wei Wang 1 2,  Haojie Zhang 1 2,  Si Zhang 3,  Youru Wu 1 2,  Jiangfan Chen 1 2,  Qingqing Yao 1 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Eye Health, Optometry and Vision Science, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.
  • 2 Zhejiang Key Laboratory of Key Technologies for Visual Pathway Reconstruction, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.
  • 3 Department of Ophthalmology, The First People's Hospital of Foshan, Foshan, Guangdong 528000, China.
PMID: 40290884 DOI: 10.1016/j.mtbio.2025.101757
Abstract

Neovascular age-related macular degeneration (nAMD) has become the leading cause of vision loss in people over 60 years old. Anti-vascular endothelial growth factor (anti-VEGF), the current first-line drug for the treatment of nAMD, suffers from poor patient compliance and fundus fibrosis scar formation. In addition to VEGF, oxidative stress and inflammation also play key roles in the pathological process of choroidal neovascularization (CNV). Therefore, combinational therapeutics with anti-angiogenic, Reactive Oxygen Species (ROS)-scavenging and anti-inflammatory functions will broaden therapeutic effects and reduce side effects. The Yes-associated protein-1 (YAP) has proven to inhibit angiogenesis, inflammation, and subretinal fibrosis in CNV. Herein, verteporfin (VP), the inhibitor of YAP, was encapsulated into a polydopamine modified mesoporous silica nanoparticle (PMSN-VP NPs) and then conjugated with PLGA-PEG-PBA decorated cerium oxide nanoparticles (PPCeO2 NPs) to develop an integrated nano-drug delivery system. The PMSN-VP@PPCeO2 NPs exhibited ROS-responsive degradation and VP release behaviors, and our in vitro data revealed that the PMSN-VP@PPCeO2 NPs downregulated angiogenic-related and fibrosis-related gene expressions in human umbilical vein endothelial cells (HUVECs) and further showed excellent anti-oxidative and anti-inflammatory capacities in BV2 cells. More importantly, the PMSN-VP@PPCeO2 NPs significantly suppressed vascular leakage and macrophage infiltration in the laser-induced CNV lesions of mice. Overall, our findings demonstrated that the PMSN-VP@PPCeO2 NPs provided an effective therapeutic strategy for nAMD.

Keywords

Age-related macular degeneration; Anti-angiogenic; Integrated nano-drug delivery system; ROS-Scavenging; Yes-associated protein-1.

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