Isabel S Oliveira, Sandra G Silva, Andreia C Gomes, M Elisabete C D Real Oliveira, M Luísa C do Vale, Eduardo F Marques
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Herein, we investigated the DNA complexation ability of mixtures of serine-based gemini surfactants, (nSer)<sub>2</sub>N5, and monoolein (MO) as a helper lipid. The micelle-forming serine surfactants contain long lipophilic chains (12 to 18 C atoms) and a five CH<sub>2</sub> spacer, both linked to the nitrogen atoms of the serine residues by amine linkages. The (nSer)<sub>2</sub>N5:MO aggregates are non-cytotoxic up to 35-90 µM, depending on surfactant and surfactant/MO mixing ratio, and in general, higher MO content and longer surfactant chain length tend to promote higher cell viability. All systems efficaciously complex DNA, but the (18Ser)<sub>2</sub>N5:MO one clearly stands as the best-performing one. Incorporating MO into the serine surfactant system affects the morphology and size distribution of the formed mixed aggregates. In the low concentration regime, gemini-MO systems aggregate in the form of vesicles, while at high concentrations the formation of a lamellar liquid crystalline phase is observed. 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引用次数: 0
摘要
阳离子双子表面活性剂由于具有很强的静电结合能力,可以与 DNA 共同结合,因此已成为潜在的基因递送剂。通常情况下,加入辅助脂质(HL)会增强 DNA 的复合性,辅助脂质在转染效率方面也起着关键作用。作为非病毒载体用于转染的脂质体通过静电和疏水相互作用的形成受到各种理化参数的影响,如阳离子表面活性剂:HL 摩尔比、(+/-)电荷比以及脂质体的形态结构。在此,我们研究了丝氨酸基双子表面活性剂 (nSer)2N5 和作为辅助脂质的单油脂 (MO) 混合物的 DNA 复配能力。形成胶束的丝氨酸表面活性剂含有长亲脂性链(12 到 18 个 C 原子)和一个 5 CH2 的间隔物,两者都通过胺连接与丝氨酸残基的氮原子相连。(nSer)2N5:MO聚合体的无毒性可达 35-90 µM,具体取决于表面活性剂和表面活性剂/MO 的混合比例,一般来说,MO 含量越高、表面活性剂链长越长,细胞的存活率就越高。所有系统都能有效地复合 DNA,但(18Ser)2N5:MO 显然是效果最好的一种。在丝氨酸表面活性剂体系中加入 MO 会影响所形成的混合聚集体的形态和大小分布。在低浓度条件下,gemini-MO 系统以囊泡形式聚集,而在高浓度条件下,则会形成片状液晶相。这表明脂联素可能具有类似的基于双分子层的结构。
Cationic Serine-Based Gemini Surfactant:Monoolein Aggregates as Viable and Efficacious Agents for DNA Complexation and Compaction: A Cytotoxicity and Physicochemical Assessment.
Cationic gemini surfactants have emerged as potential gene delivery agents as they can co-assemble with DNA due to a strong electrostatic association. Commonly, DNA complexation is enhanced by the inclusion of a helper lipid (HL), which also plays a key role in transfection efficiency. The formation of lipoplexes, used as non-viral vectors for transfection, through electrostatic and hydrophobic interactions is affected by various physicochemical parameters, such as cationic surfactant:HL molar ratio, (+/-) charge ratio, and the morphological structure of the lipoplexes. Herein, we investigated the DNA complexation ability of mixtures of serine-based gemini surfactants, (nSer)2N5, and monoolein (MO) as a helper lipid. The micelle-forming serine surfactants contain long lipophilic chains (12 to 18 C atoms) and a five CH2 spacer, both linked to the nitrogen atoms of the serine residues by amine linkages. The (nSer)2N5:MO aggregates are non-cytotoxic up to 35-90 µM, depending on surfactant and surfactant/MO mixing ratio, and in general, higher MO content and longer surfactant chain length tend to promote higher cell viability. All systems efficaciously complex DNA, but the (18Ser)2N5:MO one clearly stands as the best-performing one. Incorporating MO into the serine surfactant system affects the morphology and size distribution of the formed mixed aggregates. In the low concentration regime, gemini-MO systems aggregate in the form of vesicles, while at high concentrations the formation of a lamellar liquid crystalline phase is observed. This suggests that lipoplexes might share a similar bilayer-based structure.
期刊介绍:
Journal of Functional Biomaterials (JFB, ISSN 2079-4983) is an international and interdisciplinary scientific journal that publishes regular research papers (articles), reviews and short communications about applications of materials for biomedical use. JFB covers subjects from chemistry, pharmacy, biology, physics over to engineering. The journal focuses on the preparation, performance and use of functional biomaterials in biomedical devices and their behaviour in physiological environments. Our aim is to encourage scientists to publish their results in as much detail as possible. Therefore, there is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Several topical special issues will be published. Scope: adhesion, adsorption, biocompatibility, biohybrid materials, bio-inert materials, biomaterials, biomedical devices, biomimetic materials, bone repair, cardiovascular devices, ceramics, composite materials, dental implants, dental materials, drug delivery systems, functional biopolymers, glasses, hyper branched polymers, molecularly imprinted polymers (MIPs), nanomedicine, nanoparticles, nanotechnology, natural materials, self-assembly smart materials, stimuli responsive materials, surface modification, tissue devices, tissue engineering, tissue-derived materials, urological devices.