用于肿瘤免疫治疗的适体功能化靶向siRNA递送系统。

IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Biomedical materials Pub Date : 2022-02-09 DOI:10.1088/1748-605X/ac5382
Haiyin Lv, Tengfei Wang, F. Ma, Kunchi Zhang, Tian Gao, R. Pei, Ye Zhang
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引用次数: 4

摘要

程序性死亡配体1 (Programmed death ligand 1, PD-L1)在肿瘤细胞表面过表达是肿瘤免疫逃逸的原因之一。降低PD-L1的表达已被证明是促进免疫系统激活和抑制肿瘤进展的有效策略。RNA干扰(RNAi)是一种很有前途的肿瘤基因调控技术。本研究构建靶向siRNA传递系统NPs@apt,将PD-L1 siRNA转染人非小细胞肺癌细胞系(A549),抑制肿瘤免疫逃逸。用阳离子Lipofectamine 2000压缩PD-L1 siRNA,与红细胞膜源性纳米囊泡融合,并进一步靶向AS1411适配体修饰,制备NPs@apt。红细胞膜的引入使siRNA传递系统具有较低的细胞毒性和逃避巨噬细胞吞噬的能力。证实了NPs@apt的稳定性和对负载siRNA的保护作用。NPs@apt处理后的体外研究表明,PD-L1 siRNA被选择性地递送到A549细胞中,并进一步导致PD-L1基因敲低、T细胞活化和肿瘤细胞生长抑制。本研究为特异性siRNA转染提高抗肿瘤免疫提供了一种替代策略。
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Aptamer-functionalized targeted siRNA delivery system for tumor immunotherapy.
Programmed death ligand 1 (PD-L1) overexpressed on the surface of tumor cells is one of the reasons for tumor immune escape. Reducing PD-L1 expression has been proved to be an effective strategy to facilitate immune system activation and inhibit tumor progression. RNA interference (RNAi) is a promising technology for gene regulation in tumor therapy. In this study, we constructed a targeted siRNA delivery system NPs@apt to transfect PD-L1 siRNA into human non-small-cell lung carcinoma cell line (A549) for inhibiting tumor immune evasion. NPs@apt was prepared by compressing PD-L1 siRNA with cationic Lipofectamine 2000, fusing with erythrocyte membrane-derived nanovesicles, and further modifying with targeting AS1411 aptamer. The introduction of erythrocyte membrane endows the siRNA delivery system with lower cytotoxicity and the ability to escape from the phagocytosis of macrophages. The stability of NPs@apt and the protection to loaded siRNA were confirmed. In vitro studies after NPs@apt treatment demonstrated that PD-L1 siRNA was selectively delivered into A549 cells, and further resulted in PD-L1 gene knockdown, T cell activation and tumor cell growth inhibition. This study offers an alternative strategy for specific siRNA transfection for improving anti-tumor immunity.
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来源期刊
Biomedical materials
Biomedical materials 工程技术-材料科学:生物材料
CiteScore
6.70
自引率
7.50%
发文量
294
审稿时长
3 months
期刊介绍: The goal of the journal is to publish original research findings and critical reviews that contribute to our knowledge about the composition, properties, and performance of materials for all applications relevant to human healthcare. Typical areas of interest include (but are not limited to): -Synthesis/characterization of biomedical materials- Nature-inspired synthesis/biomineralization of biomedical materials- In vitro/in vivo performance of biomedical materials- Biofabrication technologies/applications: 3D bioprinting, bioink development, bioassembly & biopatterning- Microfluidic systems (including disease models): fabrication, testing & translational applications- Tissue engineering/regenerative medicine- Interaction of molecules/cells with materials- Effects of biomaterials on stem cell behaviour- Growth factors/genes/cells incorporated into biomedical materials- Biophysical cues/biocompatibility pathways in biomedical materials performance- Clinical applications of biomedical materials for cell therapies in disease (cancer etc)- Nanomedicine, nanotoxicology and nanopathology- Pharmacokinetic considerations in drug delivery systems- Risks of contrast media in imaging systems- Biosafety aspects of gene delivery agents- Preclinical and clinical performance of implantable biomedical materials- Translational and regulatory matters
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