题目： | Enzyme-Responsive DNA Origami-Antibody Conjugates for Targeted and Combined Therapy of Choroidal Neovascularization |
作者： | Yuqi Wu1#, Xuan Qin1#, Xing Lu1#, Chen Ji1, Yufan Ling2, Jiawei Zhang1, Haoliang Shi1, Binbin Chu1, Bin Song1, Houyu Wang1*, and Yao He1,3* |
单位： | 1Suzhou Key Laboratory of Nanotechnology and Biomedicine, Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Institute of Functional Nano and Soft Materials (FUNSOM) and Collaborative Innovation Center of Suzhou Nano Science and Technology (NANO-CIC), Soochow University, Suzhou 215123, China. 2State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, China. 3Macao Translational Medicine Center and Macao Institute of Materials Science and Engineering, Macau University of Science and Technology, 999078 Macau SAR, China. |
摘要： | Monotherapy, especially the use of antibodies targeting vascular endothelial growth factor (VEGF), has shown limitations in treating choroidal neovascularization (CNV) since reactive oxygen species (ROS) also exacerbate CNV formation. Herein, we developed a combination therapy based on a DNA origami platform targeting multiple components of ocular neovascularization. Our study demonstrated that ocular neovascularization was markedly suppressed by intravitreal injection of a rectangular DNA origami sheet modified with VEGF aptamers (Ap) conjugated to an anti-VEGF antibody (aV) via matrix metalloproteinase (MMP)-cleavable peptide linkers in a mouse model of CNV. Typically, the DNA origami-based therapeutic platform selectively accumulates in neovascularization lesions owing to the dual-targeting ability of the aV and Ap, followed by the cleavage of the peptide linker by MMPs to release the antibody. Together, the released antibody and Ap inhibited VEGF activity. Moreover, the residual bare DNA origami could effectively scavenge ROS, reducing oxidative stress at CNV sites and thus maximizing the synergistic effects of inhibiting neovascularization. |
影响因子： | 15.8 |
分区情况： | 一区 |
链接： | https://doi.org/10.1021/acsnano.4c05635 责任编辑：杜欣 |