cKK-E12是一种可用于形成脂质纳米颗粒（LNP）以高效传递siRNA和mRNA的可电离脂质。
Cas No.:1432494-65-9
Sample solution is provided at 25 µL, 10mM.
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cKK-E12 is an ionizable lipid that can be used to form lipid nanoparticles (LNP) for efficient delivery of siRNA and mRNA[1]. LNP formed with cKK-E12 exhibit high surface binding affinity for endogenous apolipoprotein E (ApoE), demonstrating strong tropism for hepatocytes[2]. cKK-E12 is commonly applied in targeted gene delivery and therapy, vaccine development, molecular imaging, and related fields[3,4].
In vitro, treatment of RAW 264.7 macrophages with cKK-E12 LNP (400ng/mL) for 6h significantly upregulates the expression of pro-inflammatory cytokines IL-6, TNF-α, IL-1α, IFN-β, and the chemokine MCP-1. Furthermore, treatment with cKK-E12 LNP (400ng/mL) for 24h markedly increases the proportions of apoptotic, necrotic, and pyroptotic cells[5].
In vivo, administration of Cy5-labeled mRNA-loaded cKK-E12 LNP (0.75mg/kg) via tail vein injection in C57BL/6 mice results in predominant accumulation in the liver (>60%) within 1h, followed by the spleen, lungs, and kidneys[6]. Intravenous injection of trastuzumab mRNA-loaded cKK-E12 LNP (0.5, 1, and 2mg/kg) in C57BL/6 mice leads to a dose-dependent increase in serum trastuzumab levels after 24h, reaching approximately 40µg/mL at the 2mg/kg dose[7].
References:
[1] ZENG Y, ESCALONA-RAYO O, KNOL R, et al. Lipid nanoparticle-based mRNA candidates elicit potent T cell responses[J]. Biomaterials Science, 2023, 11(3): 964-974.
[2] DONG Y, LOVE K T, DORKIN J R, et al. Lipopeptide nanoparticles for potent and selective siRNA delivery in rodents and nonhuman primates[J]. Proceedings of the National Academy of Sciences, 2014, 111(11): 3955-3960.
[3] FENTON O S, KAUFFMAN K J, MCCLELLAN R L, et al. Bioinspired alkenyl amino alcohol ionizable lipid materials for highly potent in vivo mRNA delivery[J]. Advanced Materials (Deerfield Beach, Fla.), 2016, 28(15): 2939.
[4] GORDON A, LI B, WITTEN J, et al. Inhalable dry powders for lung mRNA delivery[J]. Advanced Healthcare Materials, 2024, 13(29): 2400509.
[5] OMO-LAMAI S, WANG Y, PATEL M N, et al. Lipid nanoparticle-associated inflammation is triggered by sensing of endosomal damage: engineering endosomal escape without side effects[J]. bioRxiv, 2024: 2024.04.16.589801.
[6] MELAMED J R, HAJJ K A, CHAUDHARY N, et al. Lipid nanoparticle chemistry determines how nucleoside base modifications alter mRNA delivery[J]. Journal of Controlled Release, 2022, 341: 206-214.
[7] RYBAKOVA Y, KOWALSKI P S, HUANG Y, et al. mRNA delivery for therapeutic anti-HER2 antibody expression in vivo[J]. Molecular Therapy, 2019, 27(8): 1415-1423.
cKK-E12是一种可用于形成脂质纳米颗粒（LNP）以高效传递siRNA和mRNA的可电离脂质[1]。cKK-E12形成的LNP表面可高效结合内源性载脂蛋白E（ApoE），对肝实质细胞具有极强的亲和力[2]。cKK-E12通常用于靶向基因的递送与治疗、疫苗研发及分子成像等领域[3,4]。
在体外，cKK-E12 LNP（400ng/mL）处理RAW 264.7巨噬细胞6h，显著上调了促炎细胞因子IL-6、TNF-α、IL-1α、IFN-β和趋化因子MCP-1的表达。cKK-E12 LNP（400ng/mL）处理RAW 264.7巨噬细胞24h，可显著增加凋亡、坏死和焦亡细胞的比例[5]。
在体内，Cy5标记mRNA的cKK-E12 LNP（0.75mg/kg）通过尾静脉注射处理C57BL/6小鼠，1h后cKK-E12 LNP主要积累于肝脏（＞60%），其次为脾、肺和肾[6]。载有曲妥珠单抗mRNA的cKK-E12 LNP（0.5, 1, 2mg/kg）通过静脉注射处理C57BL/6小鼠，24h后血清中曲妥珠单抗呈剂量依赖性增加，2mg/kg剂量下血清浓度达约40μg/mL[7]。
| Cell experiment [1]: | |
Cell lines | RAW 264.7 macrophages |
Preparation Method | RAW 264.7 macrophages were treated with cKK-E12 LNP at a dose of 400ng/mL of mRNA for 6h, and the concentrations of pro-inflammatory cytokines (IL-6, TNF-α, IL-1α, IFN-β) and chemokine MCP-1 in the supernatant were measured using a multiplex cytokine assay. |
Reaction Conditions | 400ng/mL; 6h |
Applications | cKK-E12 LNP treatment significantly upregulated the expression of pro-inflammatory cytokines IL-6, TNF-α, IL-1α, IFN-β and chemokine MCP-1. |
| Animal experiment [2]: | |
Animal models | C57BL/6 mice |
Preparation Method | C57BL/6 mice were injected via tail vein with cKK-E12 LNP encapsulating Cy5-labeled mRNA (dose 0.75mg/kg). 1h post-injection, mice were sacrificed, and major organs (liver, spleen, lungs, and kidneys) were harvested and subjected to ex vivo fluorescence imaging using an IVIS imaging system (Ex/Em: 649/670nm). Percent biodistribution was calculated for each organ based on total radiant efficiency analyzed via region of interest using Living Image software. |
Dosage form | 0.75mg/kg; i.v. |
Applications | Most cKK-E12 LNP accumulated in the liver (>60%) and, to a lesser extent, the spleen, kidneys, and lungs. |
References: | |
| Cas No. | 1432494-65-9 | SDF | Download SDF |
| Canonical SMILES | O=C1NC(CCCCN(CC(CCCCCCCCCC)O)CC(CCCCCCCCCC)O)C(NC1CCCCN(CC(CCCCCCCCCC)O)CC(CCCCCCCCCC)O)=O | ||
| 分子式 | C60H120N4O6 | 分子量 | 993.6 |
| 溶解度 | DMSO : 50 mg/mL (50.32 mM; Need ultrasonic) | 储存条件 | -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.0064 mL | 5.0322 mL | 10.0644 mL |
| 5 mM | 201.3 μL | 1.0064 mL | 2.0129 mL |
| 10 mM | 100.6 μL | 503.2 μL | 1.0064 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >95.00% Appearance: A liquid
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