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载有二甲双胍的 Netrin-1 单克隆抗体功能化纳米颗粒可预防腹主动脉瘤的进展
Authors Zhang Z, Zhuang J, Sun D, Ding Q, Zheng H, Li H, Zhang X, Du Y, Ma T, Meng Q
Received 10 December 2022
Accepted for publication 1 February 2023
Published 6 February 2023 Volume 2023:18 Pages 627—639
DOI https://doi.org/10.2147/IJN.S400993
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Yan Shen
Background: Abdominal aortic aneurysms (AAAs) are a global health and economic burden. Therapeutic strategies to inhibit the progression of AAAs are currently lacking. Recently, the therapeutic effect of metformin on aneurysms has attracted considerable interest. However, the unfavorable pharmacokinetic properties of metformin limit its feasibility for AAA treatment.
Methods and Results: We constructed a metformin-loaded netrin-1-responsive AAA-targeted nanoparticle (Tgt-NP-Met) for AAA management. Evaluation of the therapeutic effect of Tgt-NP-Met was performed by in vitro and in vivo experiments. Our results showed that the binding of netrin-1 monoclonal antibodies enhanced the AAA-targeting capability of nanoparticles (NPs). Moreover, Tgt-NP-Met administration prevented AAA development and reduced the aneurysm diameter in apolipoprotein E (ApoE)-deficient (ApoE−/−) mice that received continuous infusion of angiotensin II. Furthermore, metformin prevented AAA progression by inhibiting the transformation of vascular smooth muscle cells (VSMCs) from a contractile phenotype to a synthetic phenotype, which is mediated by macrophage infiltration and activation.
Conclusion: Our findings identify metformin as a functional suppressor for macrophage-mediated phenotypic transformation of VSMCs and Tgt-NP-Met as an efficient therapeutic strategy for AAA management.
Keywords: abdominal aortic aneurysm, nanoparticle, metformin, macrophage