M2-type macrophage-targeted delivery of IKKβ siRNA induces M2-to-M1 repolarization for CNV gene therapy

IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Nanomedicine : nanotechnology, biology, and medicine Pub Date : 2024-03-06 DOI:10.1016/j.nano.2024.102740
Yu Zhang MD , Baorui Chu MD , Qian Fan MD , Xian Song MD , Qian Xu MD , Yi Qu MD
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Abstract

Choroidal Neovascularization (CNV) is capable of inciting recurrent hemorrhage in the macular region, severely impairing patients' visual acuity. During the onset of CNV, infiltrating M2 macrophages play a crucial role in promoting angiogenesis.

To control this disease, our study utilizes the RNA interference (RNAi)-based gene therapy to reprogram M2 macrophages to the M1 phenotype in CNV lesions. We synthesize the mannose-modified siRNA-loaded liposome specifically targeting M2 macrophages to inhibit the inhibitory kappa B kinase β (IKKβ) gene involved in the polarization of macrophages, consequently modulating macrophage polarization state. In vitro and in vivo, the mannose-modified IKKβ siRNA-loaded liposome (siIKKβ-ML) has been proven to effectively target M2 macrophages to repolarize them to M1 phenotype, and inhibit the progression of CNV. Collectively, our findings elucidate that siIKKβ-ML holds the potential to control CNV by reprogramming the macrophage phenotype, indicating a promising therapeutic avenue for CNV management.

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M2型巨噬细胞靶向递送IKKβ siRNA可诱导M2-M1再极化,用于CNV基因治疗。
脉络膜新生血管(CNV)可导致黄斑区反复出血,严重损害患者的视力。在 CNV 的发病过程中,浸润的 M2 巨噬细胞在促进血管生成方面起着至关重要的作用。为了控制这种疾病,我们的研究利用基于 RNA 干扰(RNAi)的基因疗法将 CNV 病变中的 M2 巨噬细胞重编程为 M1 表型。我们合成了甘露糖修饰的 siRNA 脂质体,专门靶向 M2 巨噬细胞,抑制参与巨噬细胞极化的抑制性卡巴 B 激酶 β(IKKβ)基因,从而调节巨噬细胞的极化状态。在体外和体内,甘露糖修饰的 IKKβ siRNA 载体脂质体(siIKKβ-ML)已被证实能有效靶向 M2 巨噬细胞,使其重新极化为 M1 表型,并抑制 CNV 的进展。总之,我们的研究结果阐明,siIKKβ-ML 有可能通过重编程巨噬细胞表型来控制 CNV,为 CNV 的治疗提供了一条前景广阔的途径。
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来源期刊
CiteScore
11.10
自引率
0.00%
发文量
133
审稿时长
42 days
期刊介绍: The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine. Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.
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