N/P 比对聚乙二醇化聚[2-（二甲氨基）乙基甲基丙烯酸酯]基 siRNA 复合物的体内外相互作用特性的影响。
The effect of N/P ratio on the in vitro and in vivo interaction properties of PEGylated poly[2-(dimethylamino)ethyl methacrylate]-based siRNA complexes.
机构信息
School of Chemical Engineering, Purdue University, West Lafayette, Indiana, 47907, USA.
出版信息
Macromol Biosci. 2013 Aug;13(8):1059-71. doi: 10.1002/mabi.201300046. Epub 2013 Jul 5.
Abstract
PEG-PnBA-PDMAEMA triblock and PEG-PDMAEMA diblock copolymers are used as model systems for studying the role of N/P ratio on the in vivo behavior of PEGylated siRNA carriers in mice. The presence of a free/uncomplexed polymer population coexisting with siRNA complexes is established. A change in the N/P ratio exerts no significant influence on the in vivo biodistribution and ex vivo blood chemistry properties of the respective systems. Histological analysis of major organs indicates that the presence of uncomplexed polymer elicits toxicity to the organ that is associated with the clearance of the siRNA complexes from the circulation system. This effect can be eliminated by working at N/P ratios near the charge-neutralization point of the complexes.
摘要
PEG-PnBA-PDMAEMA 三嵌段共聚物和 PEG-PDMAEMA 二嵌段共聚物被用作研究 N/P 比对 PEG 化 siRNA 载体在小鼠体内行为影响的模型系统。已经确定了游离/未复合聚合物群体与 siRNA 复合物共存的情况。N/P 比的变化对各体系的体内生物分布和体外血液化学性质没有显著影响。主要器官的组织学分析表明，未复合聚合物的存在会对器官产生毒性，这与 siRNA 复合物从循环系统中清除有关。通过在接近复合物电荷中和点的 N/P 比下工作，可以消除这种影响。
相似文献
1
The effect of N/P ratio on the in vitro and in vivo interaction properties of PEGylated poly[2-(dimethylamino)ethyl methacrylate]-based siRNA complexes.N/P 比对聚乙二醇化聚[2-（二甲氨基）乙基甲基丙烯酸酯]基 siRNA 复合物的体内外相互作用特性的影响。
Macromol Biosci. 2013 Aug;13(8):1059-71. doi: 10.1002/mabi.201300046. Epub 2013 Jul 5.
2
Effects of the incorporation of a hydrophobic middle block into a PEG-polycation diblock copolymer on the physicochemical and cell interaction properties of the polymer-DNA complexes.将疏水性中间嵌段引入聚乙二醇-聚阳离子二嵌段共聚物对聚合物-脱氧核糖核酸复合物的物理化学性质和细胞相互作用特性的影响。
Biomacromolecules. 2008 Nov;9(11):3294-307. doi: 10.1021/bm800876v. Epub 2008 Oct 23.
3
Steric stabilization of poly(2-(dimethylamino)ethyl methacrylate)-based polyplexes mediates prolonged circulation and tumor targeting in mice.基于聚甲基丙烯酸2-（二甲氨基）乙酯的多聚体的空间稳定作用介导了其在小鼠体内的长循环和肿瘤靶向性。
J Gene Med. 2004 Jan;6(1):64-75. doi: 10.1002/jgm.475.
4
PEGylated poly(2-(dimethylamino) ethyl methacrylate)/DNA polyplex micelles decorated with phage-displayed TGN peptide for brain-targeted gene delivery.聚乙二醇化聚（2-二甲氨基乙基甲基丙烯酸酯）/噬菌体展示靶向转甲状腺素蛋白囊泡肽修饰的 DNA 高分子复合胶束用于脑靶向基因递释。
Biomaterials. 2013 Mar;34(8):2117-29. doi: 10.1016/j.biomaterials.2012.11.050. Epub 2012 Dec 13.
5
Structural contributions of blocked or grafted poly(2-dimethylaminoethyl methacrylate) on PEGylated polycaprolactone nanoparticles in siRNA delivery.受阻或接枝聚(2-二甲氨基乙基甲基丙烯酸酯)对聚乙二醇化聚己内酯纳米粒在 siRNA 递送中的结构贡献。
Biomaterials. 2011 Nov;32(33):8730-42. doi: 10.1016/j.biomaterials.2011.07.089. Epub 2011 Sep 1.
6
Reversibly shielded DNA polyplexes based on bioreducible PDMAEMA-SS-PEG-SS-PDMAEMA triblock copolymers mediate markedly enhanced nonviral gene transfection.基于生物可还原 PDMAEMA-SS-PEG-SS-PDMAEMA 三嵌段共聚物的可逆屏蔽 DNA 超分子复合物介导显著增强的非病毒基因转染。
Biomacromolecules. 2012 Mar 12;13(3):769-78. doi: 10.1021/bm201693j. Epub 2012 Feb 10.
7
Efficient intracellular siRNA delivery strategy through rapid and simple two steps mixing involving noncovalent post-PEGylation.通过涉及非共价的 PEG 化后两步快速简单混合实现高效的细胞内 siRNA 传递策略。
J Control Release. 2009 Sep 1;138(2):141-7. doi: 10.1016/j.jconrel.2009.04.034. Epub 2009 May 6.
8
Local release of siRNA using polyplex-loaded thermosensitive hydrogels.利用载有 siRNA 的聚电解质复合物的温敏水凝胶实现局部释放。
Nanoscale. 2020 May 14;12(18):10347-10360. doi: 10.1039/d0nr03147j.
9
Polycation-detachable nanoparticles self-assembled from mPEG-PCL-g-SS-PDMAEMA for in vitro and in vivo siRNA delivery.由 mPEG-PCL-g-SS-PDMAEMA 自组装而成的聚阳离子可分离纳米颗粒用于体外和体内 siRNA 递送。
Acta Biomater. 2013 Aug;9(8):7746-57. doi: 10.1016/j.actbio.2013.04.031. Epub 2013 Apr 25.
10
Combinatorial optimization of PEG architecture and hydrophobic content improves ternary siRNA polyplex stability, pharmacokinetics, and potency in vivo.聚乙二醇（PEG）结构与疏水含量的组合优化可提高三元小干扰RNA（siRNA）多聚体的稳定性、药代动力学及体内效能。
J Control Release. 2017 Jun 10;255:12-26. doi: 10.1016/j.jconrel.2017.03.389. Epub 2017 Mar 31.
引用本文的文献
1
Self-assembled extracellular matrix-lipid nanoparticle composite for site-specific siRNA delivery to improve cardiac repair post-myocardial infarction.用于将小干扰RNA（siRNA）特异性递送至心肌梗死部位以促进心脏修复的自组装细胞外基质-脂质纳米颗粒复合物
Mater Today Bio. 2025 Aug 15;34:102205. doi: 10.1016/j.mtbio.2025.102205. eCollection 2025 Oct.
2
Drug delivery agent that acts as a drug for synergistic activity.作为具有协同活性药物的药物递送剂。
iScience. 2025 Jun 13;28(8):112890. doi: 10.1016/j.isci.2025.112890. eCollection 2025 Aug 15.
3
Modulation of lipid nanoparticle-formulated plasmid DNA drives innate immune activation promoting adaptive immunity.脂质纳米颗粒包裹的质粒DNA的调控驱动先天免疫激活，促进适应性免疫。
Cell Rep Med. 2025 Apr 15;6(4):102035. doi: 10.1016/j.xcrm.2025.102035. Epub 2025 Mar 21.
4
Rescue of the endogenous FVIII expression in hemophilia A mice using CRISPR-Cas9 mRNA LNPs.使用CRISPR-Cas9 mRNA脂质纳米颗粒挽救A型血友病小鼠的内源性FVIII表达。
Mol Ther Nucleic Acids. 2024 Nov 6;35(4):102383. doi: 10.1016/j.omtn.2024.102383. eCollection 2024 Dec 10.
5
Molecular Dynamics Simulations Elucidate the Molecular Organization of Poly(beta-amino ester) Based Polyplexes for siRNA Delivery.分子动力学模拟阐明了用于小干扰RNA递送的基于聚（β-氨基酯）的多聚体的分子组织。
Nano Lett. 2024 Dec 11;24(49):15683-15692. doi: 10.1021/acs.nanolett.4c04291. Epub 2024 Nov 26.
6
CRISPR/Cas9 Mutagenesis through Introducing a Nanoparticle Complex Made of a Cationic Polymer and Nucleic Acids into Maize Protoplasts.通过将由阳离子聚合物和核酸组成的纳米颗粒复合物导入玉米原生质体进行 CRISPR/Cas9 诱变。
Int J Mol Sci. 2023 Nov 9;24(22):16137. doi: 10.3390/ijms242216137.
7
Development and Characterization of an In Vitro Cell-Based Assay to Predict Potency of mRNA-LNP-Based Vaccines.一种基于体外细胞检测法预测基于mRNA-LNP疫苗效力的方法的开发与特性研究
Vaccines (Basel). 2023 Jul 10;11(7):1224. doi: 10.3390/vaccines11071224.
8
Ionizable Lipid Nanoparticles for Therapeutic Base Editing of Congenital Brain Disease.用于治疗性先天性脑疾病碱基编辑的可离子化脂质纳米颗粒。
ACS Nano. 2023 Jul 25;17(14):13594-13610. doi: 10.1021/acsnano.3c02268. Epub 2023 Jul 17.
9
The Effect of Ethanol on Lipid Nanoparticle Stabilization from a Molecular Dynamics Simulation Perspective.从分子动力学模拟角度看乙醇对脂质纳米粒子稳定性的影响。
Molecules. 2023 Jun 17;28(12):4836. doi: 10.3390/molecules28124836.
10
Liposomal Delivery of MIW815 (ADU-S100) for Potentiated STING Activation.用于增强STING激活的MIW815（ADU-S100）的脂质体递送
Pharmaceutics. 2023 Feb 14;15(2):638. doi: 10.3390/pharmaceutics15020638.
本文引用的文献
1
Elucidating the interplay between DNA-condensing and free polycations in gene transfection through a mechanistic study of linear and branched PEI.通过对线性和支化的聚乙烯亚胺的机理研究阐明 DNA 缩合和游离多聚阳离子在基因转染中的相互作用。
Biomaterials. 2011 Nov;32(33):8626-34. doi: 10.1016/j.biomaterials.2011.07.044. Epub 2011 Sep 1.
2
Revisit complexation between DNA and polyethylenimine--effect of length of free polycationic chains on gene transfection.重新考察 DNA 与聚亚乙基亚胺之间的络合作用-游离聚阳离子链长度对基因转染的影响。
J Control Release. 2011 May 30;152(1):143-51. doi: 10.1016/j.jconrel.2011.03.020. Epub 2011 Mar 30.
3
Influence of nano-carrier architecture on in vitro siRNA delivery performance and in vivo biodistribution: polyplexes vs micelleplexes.纳米载体结构对体外 siRNA 递送性能和体内分布的影响：聚合物胶束与胶束复合物。
ACS Nano. 2011 May 24;5(5):3493-505. doi: 10.1021/nn102540y. Epub 2011 Apr 6.
4
A discussion of the pH-dependent protonation behaviors of poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) and poly(ethylenimine-ran-2-ethyl-2-oxazoline) (P(EI-r-EOz)).讨论聚(2-(二甲氨基)乙基甲基丙烯酸酯) (PDMAEMA) 和聚(乙撑亚胺-ran-2-乙基-2-恶唑啉) (P(EI-r-EOz)) 的 pH 依赖质子化行为。
J Phys Chem B. 2011 Feb 10;115(5):844-60. doi: 10.1021/jp109151s. Epub 2011 Jan 6.
5
Strategies in the design of nanoparticles for therapeutic applications.用于治疗应用的纳米粒子设计策略。
Nat Rev Drug Discov. 2010 Aug;9(8):615-27. doi: 10.1038/nrd2591. Epub 2010 Jul 9.
6
Co-delivery of siRNA and paclitaxel into cancer cells by biodegradable cationic micelles based on PDMAEMA-PCL-PDMAEMA triblock copolymers.基于 PDMAEMA-PCL-PDMAEMA 三嵌段共聚物的阳离子胶束共载 siRNA 和紫杉醇递送入癌细胞。
Biomaterials. 2010 Mar;31(8):2408-16. doi: 10.1016/j.biomaterials.2009.11.077. Epub 2009 Dec 5.
7
Folate-conjugated micelles and their folate-receptor-mediated endocytosis.叶酸偶联胶束及其叶酸受体介导的内吞作用。
Macromol Biosci. 2009 Nov 10;9(11):1059-68. doi: 10.1002/mabi.200900134.
8
Nonviral siRNA delivery to the lung: investigation of PEG-PEI polyplexes and their in vivo performance.非病毒小干扰RNA递送至肺部：聚乙二醇-聚乙烯亚胺复合纳米粒及其体内性能研究
Mol Pharm. 2009 Jul-Aug;6(4):1246-60. doi: 10.1021/mp900107v.
9
Missing pieces in understanding the intracellular trafficking of polycation/DNA complexes.理解聚阳离子/DNA复合物细胞内运输过程中缺失的环节。
J Control Release. 2009 Oct 15;139(2):88-93. doi: 10.1016/j.jconrel.2009.06.031. Epub 2009 Jul 4.
10
In vivo pharmacokinetics, tissue distribution and underlying mechanisms of various PEI(-PEG)/siRNA complexes.各种聚乙烯亚胺（-聚乙二醇）/小干扰RNA复合物的体内药代动力学、组织分布及潜在机制
Toxicol Appl Pharmacol. 2009 Apr 1;236(1):97-108. doi: 10.1016/j.taap.2009.01.014. Epub 2009 Jan 29.
Zotero 插件