A cationic cholesterol
DC-Chol(hydrochloric acid) can inhibit the formation of Aβ40 fibers,DC-Chol(hydrochloric acid) can inhibit the amyloid formation of oxidized hCT[1,2].
For DC-Chol (hydrochloride), Aβ fibers were observed in the image of Aβ40 (30 μM) coincubated with low concentration of DC-Chol (hydrochloride) (50 ng/mL). However, in the presence of 500 μg/mL DC-Chol (hydrochloride), no fiber structures were found in the image[1]. DC-Chol/DOPE cationic liposomes properly condense and compact CT-DNA by means of a strong entropically driven surface electrostatic interaction[3]. Lipoplexes constituted by calf-thymus DNA (CT-DNA) and mixed cationic liposomes consisting of varying proportions of the cationic lipid 3β-[N-(N',N'-dimethylaminoethane)-carbamoyl]cholesterol hydrochloride (DC-Chol (hydrochloride)) and DOPE have been analyzed. DC-Chol/DOPE liposomes, with a mean hydrodynamic diameter of around (120±10) nm, compact and condense DNA fragments at their cationic surfaces by means of a strong entropically driven electrostatic interaction[4]. Formulations prepared with 50 mol% DODAC or DC-Chol (hydrochloride), and 20 mol% DSPE-PEG(2000) exhibited circulation half-lives ranging from 6.5 to 12.5 h. DC-Chol (hydrochloride) formulations prepared with DSPE-PEG(2000) accumulated threefold higher in s.c. HT29 tumors than its PEG-free counterpart[6]. DC-Chol (hydrochloride) is internalized through macrocytosis and clathrin-mediated endocytosis [5].
参考文献:
[1]. Elbassal EA, Liu H, et,al. Effects of Charged Cholesterol Derivatives on Aβ40 Amyloid Formation. J Phys Chem B. 2016 Jan 14;120(1):59-68. doi: 10.1021/acs.jpcb.5b09557. Epub 2015 Dec 23. PMID: 26652010; PMCID: PMC4959543.
[2]. Lantz R, Busbee B, et,al. Effects of disulfide bond and cholesterol derivatives on human calcitonin amyloid formation. Biopolymers. 2020 May;111(5):e23343. doi: 10.1002/bip.23343. Epub 2019 Dec 5. PMID: 31804717; PMCID: PMC9254112.
[3]. Rodríguez-Pulido A, Ortega F, et,al. A physicochemical characterization of the interaction between DC-Chol/DOPE cationic liposomes and DNA. J Phys Chem B. 2008 Oct 2;112(39):12555-65. doi: 10.1021/jp804066t. Epub 2008 Aug 27. PMID: 18729499.
[4]. Mu?oz-Ubeda M, Rodríguez-Pulido A, et,al. Effect of lipid composition on the structure and theoretical phase diagrams of DC-Chol/DOPE-DNA lipoplexes. Biomacromolecules. 2010 Dec 13;11(12):3332-40. doi: 10.1021/bm1008124. Epub 2010 Nov 8. PMID: 21058732.
[5]. Rapaka H, Manturthi S, et,al. Effect of Methylation of the Hydrophilic Domain of Tocopheryl Ammonium-Based Lipids on their Nucleic Acid Delivery Properties. ACS Omega. 2022 Apr 29;7(18):15396-15403. doi: 10.1021/acsomega.1c06889. PMID: 35571792; PMCID: PMC9096827.
[6]. Ho EA, Ramsay E, et,al. Characterization of cationic liposome formulations designed to exhibit extended plasma residence times and tumor vasculature targeting properties. J Pharm Sci. 2010 Jun;99(6):2839-53. doi: 10.1002/jps.22043. PMID: 20091826.
DC-Chol(hydrochlor acid) can inhibit the formation of Aβ40 fibers,DC-Chol(hydrochlor acid) can inhibit the amyloid formation of oxidized hCT[1,2].
对于DC -Chol（盐酸盐），Aβ；在 Aβ40 (30 μM) 与低浓度 DC-Chol（盐酸盐）(50 ng/mL) 共孵育的图像中观察到纤维。然而，在 500 μg/mL DC-Chol（盐酸盐）的存在下，图像中没有发现纤维结构[1]。 DC-Chol/DOPE 阳离子脂质体通过强熵驱动的表面静电相互作用适当地浓缩和压缩 CT-DNA[3]。由小牛胸腺 DNA (CT-DNA) 和由不同比例的阳离子脂质组成的混合阳离子脂质体构成的脂质复合物 3β-[N-(N77777#39;,N77777#39;-二甲基氨基乙烷)-氨甲酰]胆固醇盐酸盐 (DC-Chol (hydrochloride) )) 和 DOPE 已经过分析。 DC-Chol/DOPE 脂质体的平均流体动力学直径约为 (120±10) nm，通过强熵驱动的静电相互作用在其阳离子表面压缩和浓缩 DNA 片段[4]。用 50 mol% DODAC 或 DC-Chol（盐酸盐）和 20 mol% DSPE-PEG(2000) 制备的制剂表现出 6.5 至 12.5 小时的循环半衰期。用 DSPE-PEG(2000) 制备的 DC-Chol（盐酸盐）制剂在 sc 中的积累高出三倍。 HT29 肿瘤优于其不含 PEG 的肿瘤[6]。 DC-Chol（盐酸盐）通过巨细胞作用和网格蛋白介导的内吞作用内化 [5]。
| Atomic Force Microscopy (AFM) [1]: | |
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Substrate |
Aβ40 |
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Preparation Method |
Aβ40 (30 μM) in pH 7.4 phosphate buffer incubated on a Speci-Mix aliquot mixer. Aβ40 in the presence of 50 ng/mL cholesterol-SO4, 500 μg/mL cholesterol-SO4, 50 ng/mL DC-Chol (hydrochloride), and 500 μg/mL DC-cholesterol |
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Reaction Conditions |
50/500 ng/mL DC-Chol (hydrochloride) with Aβ40 for 17h |
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Applications |
For DC-Chol (hydrochloride), Aβ fibers were observed in the image of Aβ40 (30 μM) coincubated with low concentration of DC-cholesterol (50 ng/mL). However, in the presence of 500 μg/mL DC-cholesterol, no fiber structures were found in the image. |
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参考文献: [1]. Elbassal EA, Liu H, et,al. Effects of Charged Cholesterol Derivatives on Aβ40 Amyloid Formation. J Phys Chem B. 2016 Jan 14;120(1):59-68. doi: 10.1021/acs.jpcb.5b09557. Epub 2015 Dec 23. PMID: 26652010; PMCID: PMC4959543. |
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