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Fabrication, modification and application of lipid nanotubes 脂质纳米管的制备、改性及应用
IF 3.4 3区 生物学 Q1 Chemistry Pub Date : 2022-10-01 DOI: 10.1016/j.chemphyslip.2022.105242
Hongmei Bi , Zeqin Chen , Liuchun Guo , Yingmei Zhang , Xinru Zeng , Liuyi Xu

The potential application of high aspect-ratio nanomaterials motivates the development of the fabrication and modification of lipid nanotubes(LNTs). To date, diverse fabricate processes and elaborate template procedures have produced suitable tubular architectures with definite dimensions and complex structures for expected functions and applications. Herein, we comprehensively summarize the fabrication of LNTs in vitro and discuss the progress made on the micro/nanomaterials fabrication using LNTs as a template, as well as the functions and possible application of a wide range of LNTs as fundamental or derivative material. In addition, the characteristics, advantages, and disadvantages of different fabrication, modification methods, and development prospects of LNTs were briefly summarized.

高纵横比纳米材料的潜在应用推动了脂质纳米管的制备和改性的发展。迄今为止,不同的制造工艺和复杂的模板程序已经生产出适合的管状结构,具有明确的尺寸和复杂的结构,以满足预期的功能和应用。在此,我们全面总结了LNTs的体外制备,并讨论了以LNTs为模板制备微纳米材料的进展,以及广泛的LNTs作为基础或衍生材料的功能和可能的应用。此外,简要总结了不同制备、改性方法的特点、优缺点,并展望了其发展前景。
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引用次数: 0
Lipidomic analysis reveals the effect of passive smoking on facial skin surface lipid in females 脂质组学分析揭示了被动吸烟对女性面部皮肤表面脂质的影响
IF 3.4 3区 生物学 Q1 Chemistry Pub Date : 2022-09-01 DOI: 10.1016/j.chemphyslip.2022.105228
Mengzhen Zhao , Keliang Fan , Jia Wang , Juan Wang , Qingqing Xu , Dandan Wei , Yuanyuan Chen , Lihong Zhou , Zhenxing Mao , Tian Chen

Background

Smoking has toxic effects on the skin and can damage it. However, few studies have focused on the lipid profile changes of facial skin surface lipids (SSL) by passive smoking.

Method

A cross-sectional analytical study was conducted on middle-aged females volunteered from Henan, China to participate in the study. A total of 20 passive smoking females and 20 non-passive smoking females were recruited for this study. The components of skin surface lipids were measured by ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF-MS). Multivariate data analysis and enrichment analysis were used to investigate the differences in facial SSL between passive and non-passive smoking females.

Result

There were 1247 lipid entities identified in facial SSL between passive and non-passive smoking females. Significant differences in composition of facial SSL were observed between the two groups. After multivariate data analysis suggested, 28 significantly different lipids were identified and classified into four classes in SSL of the female cheeks. As well as 32 significantly different lipids were obtained in SSL of the female foreheads, which included three classes of lipids. Subsequent analysis revealed that the content of fatty acids (FA) in passive smoking females was significantly reduced and the content of glycerolipids (GL) and sphingolipids (SP) increased, compared with the control group.

Conclusion

These results indicated that an increase in GLs and SPs of facial lipids and a decrease in FAs in passive smoking females. These changes in lipids might be associated with oxidative stress and interference with signaling pathways by substances in smoke. And passive smoking affected facial SSL and changed the content and metabolism of skin lipids.

吸烟对皮肤有毒害作用,会损害皮肤。然而,很少有研究关注被动吸烟对面部皮肤表面脂质(SSL)的影响。方法采用横断面分析方法,对自愿参与研究的中国河南省中年女性进行研究。本研究共招募了20名被动吸烟女性和20名非被动吸烟女性。采用超高效液相色谱-四极杆飞行时间质谱法(UPLC-QTOF-MS)测定皮肤表面脂质成分。采用多变量数据分析和富集分析探讨了被动吸烟和非被动吸烟女性面部SSL的差异。结果被动吸烟和非被动吸烟女性面部SSL共鉴定出1247个脂质实体。两组面部SSL的组成差异有统计学意义。经多变量数据分析,鉴定出28种具有显著差异的脂质,并将其分为4类。在女性额头的SSL中还获得了32种显著不同的脂质,包括3类脂质。随后的分析显示,与对照组相比,被动吸烟女性的脂肪酸(FA)含量显著降低,甘油脂(GL)和鞘脂(SP)含量升高。结论女性被动吸烟患者面部脂质GLs和SPs升高,FAs降低。脂质的这些变化可能与氧化应激和烟雾中物质对信号通路的干扰有关。被动吸烟影响面部SSL,改变皮肤脂质含量和代谢。
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引用次数: 1
A novel and easy to prepare azo-based bioreductive linker and its application in hypoxia-sensitive cationic liposomal doxorubicin: Synthesis, characterization, in vitro and in vivo studies in mice bearing C26 tumor 一种易于制备的新型偶氮基生物还原连接剂及其在低氧敏感阳离子脂质体阿霉素中的应用:C26肿瘤小鼠的合成、表征及体内外实验研究
IF 3.4 3区 生物学 Q1 Chemistry Pub Date : 2022-09-01 DOI: 10.1016/j.chemphyslip.2022.105226
Mohammad Mashreghi , Mahdi Faal Maleki , Anis Askarizadeh , Helaleh Farshchi , Leila Farhoudi , Mahda Sadat Nasrollahzadeh , Mahere Rezazade Bazaz , Farzin Hadizadeh , Mahmoud Reza Jaafari

This study designed and synthesized a cost-effective azo-based hypoxia-sensitive linker (AHSL) using commercially accessible, inexpensive raw materials and simple methods to apply in cationic nanoliposomes. Then, AHSL was post-inserted into the cationic liposome (Cat-lip), and PEG-Azo-Cat-lip was prepared and characterized using DLS. The decrease in the zeta-potential of formulation from + 18.4 mV for Cat-lip to + 6.1 mV and the increase in the size of the PEG-Azo-Cat-lip indicated the successful post insertion of AHSL into the liposomes. The Doxorubicin (Dox) release study showed that PEGylation results in a more stable PEG-Azo-Cat-lip than the Cat-lip. The increased cytotoxicity of the PEG-Azo-Cat-lip in the hypoxic condition also indicated the cleavage of the AHSL in the hypoxic environment. In vivo biodistribution using animal imaging has shown higher tumor accumulation of the MPEG-Azo-Cat-lip than Cat-lip during the 120 h of the study. The results of anti-tumor activities and biosafety of the formulations also showed the higher efficiency of the MPEG-Azo-Cat-lip compared with the Cat-lip. The results of this study indicated the antitumor efficacy of this hypoxia-sensitive which merits further investigation.

本研究设计并合成了一种具有成本效益的偶氮基低氧敏感连接剂(AHSL),该连接剂采用商业上可获得的廉价原料和简单的方法应用于阳离子纳米脂质体。然后,将AHSL后插入阳离子脂质体(Cat-lip)中,制备PEG-Azo-Cat-lip,并用DLS对其进行表征。Cat-lip的zeta电位从+ 18.4 mV降至+ 6.1 mV, peg -偶氮猫唇的大小增加,表明AHSL成功插入脂质体。阿霉素(Dox)释放研究表明,聚乙二醇化产生的peg -偶氮猫唇比猫唇更稳定。PEG-Azo-Cat-lip在缺氧条件下的细胞毒性增加也表明了AHSL在缺氧环境下的分裂。动物成像的体内生物分布显示,在研究的120小时内,MPEG-Azo-Cat-lip的肿瘤蓄积高于Cat-lip。在抗肿瘤活性和生物安全性方面,MPEG-Azo-Cat-lip的效率高于Cat-lip。本研究结果表明,这种低氧敏感植物的抗肿瘤作用值得进一步研究。
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引用次数: 1
The effect of aerobic exercise on the lipophagy of adipose tissue in obese male mice 有氧运动对肥胖雄性小鼠脂肪组织脂质吞噬的影响
IF 3.4 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-09-01 DOI: 10.1016/j.chemphyslip.2022.105225
Rendong Li , Guangkuan Li , Yan Hai , Tao Li , Yuanyuan Bian , Tie Ma

This article explores the obesity state and the changes in the level of lipophagy in adipose tissue after exercise to lose weight, so as to provide direction and basis for theoretical research on obesity prevention and control. We established a high-fat diet model of obese mice, and applied exercise intervention and intraperitoneal injection of chloroquine to inhibit autophagy. Long-term high-fat diet can cause obesity in mice, and the process of lipophagy is inhibited, which may be one of the reasons for fat accumulation. Eight weeks of aerobic exercise can effectively reduce the weight of obese mice and promote lipolysis; this process is mainly completed by lipase decomposition, in addition to require the participation of the lipophagy process.

本文探讨运动减肥后的肥胖状态及脂肪组织中脂噬水平的变化,为肥胖防治的理论研究提供方向和依据。我们建立肥胖小鼠高脂饮食模型,采用运动干预和腹腔注射氯喹抑制自噬。长期高脂饮食可引起小鼠肥胖,脂质吞噬过程受到抑制,这可能是脂肪堆积的原因之一。8周的有氧运动能有效减轻肥胖小鼠的体重,促进脂肪分解;这一过程主要是由脂肪酶分解完成的,此外还需要吸脂过程的参与。
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引用次数: 2
The effect of selected bisphenols on model erythrocyte membranes of different cholesterol content 所选双酚类物质对不同胆固醇含量模型红细胞膜的影响
IF 3.4 3区 生物学 Q1 Chemistry Pub Date : 2022-09-01 DOI: 10.1016/j.chemphyslip.2022.105224
Karolina Olechowska, Nikola Mielniczek, Katarzyna Hąc-Wydro

Bisphenols belong to the group of environmental pollutants with proven harmful impact on human red blood cells. However, the exact effect of these substances may vary depending on the lipid composition of the cell membrane, since this structure is the first barrier between the cell interior and the external environment. The aim of this work was to analyze the influence of bisphenol A (BPA), bisphenol S (BPS) and their 1:1 mixture on model human erythrocyte membranes, composed of sphingomyelin (SM), phospatidylcholine (PC) and cholesterol (Chol). Due to the postulated correlation between the content of cholesterol in biomembranes and the toxic effect of bisphenols the model systems of different sterol concentrations (10, 20 and 40 mol% of Chol) were used in the studies. In the experiments, Langmuir monolayer technique accompanied with Brewster Angle Microscopy were applied and liposome properties were investigated. The obtained findings reveal that, in the investigated range of the sterol content, the effect of BPA, namely the changes of the organization and stability of model membranes and weakening of the attractive lipid-lipid interactions, is strongly dependent on the concentration of Chol in the system. The higher the sterol content, the stronger the BPA-induced alterations in membrane properties. However taking into account the results reported previously for the system containing 33.3% of cholesterol, it seems that the relationship between the effect of BPA and the amount of Chol is not linear for higher sterol concentrations. In contrast, BPS shows a much weaker influence on model erythrocyte membranes and does not act selectively on the systems studied. The effect of a mixture of BPA and BPS is intermediate between that of BPA and BPS used separately, however, the observed effects appear to be determined only by the presence of BPA in the system. Thus, the concentration of cholesterol in human erythrocyte membranes, which depends on factors such as age or health status, may play a key role in the toxic effects of BPA but not BPS.

双酚类物质属于已证实对人体红细胞有害的一类环境污染物。然而,这些物质的确切作用可能取决于细胞膜的脂质组成,因为细胞膜结构是细胞内部和外部环境之间的第一道屏障。本研究旨在分析双酚A (BPA)、双酚S (BPS)及其1:1混合物对由鞘磷脂(SM)、胆碱(PC)和胆固醇(Chol)组成的模型人红细胞膜的影响。由于假定生物膜中胆固醇含量与双酚的毒性作用之间存在相关性,研究中使用了不同固醇浓度(10,20和40 mol%的胆固醇)的模型系统。实验采用朗缪尔单层技术和布鲁斯特角度显微镜对脂质体性质进行了研究。研究结果表明,在甾醇含量的研究范围内,BPA的影响,即改变模型膜的组织和稳定性以及削弱脂质相互作用,强烈依赖于系统中Chol的浓度。甾醇含量越高,bpa诱导的膜性质改变越强。然而,考虑到先前报告的含有33.3%胆固醇的系统的结果,似乎BPA的影响与胆固醇含量之间的关系并不是线性的,因为胆固醇浓度较高。相比之下,BPS对模型红细胞膜的影响要弱得多,并且对所研究的系统没有选择性作用。双酚a和双酚a混合物的效果介于单独使用双酚a和双酚a之间,然而,所观察到的效果似乎仅由系统中双酚a的存在决定。因此,取决于年龄或健康状况等因素的人红细胞膜中胆固醇的浓度可能在BPA的毒性作用中起关键作用,而不是BPS。
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引用次数: 1
Experimental and theoretical investigations into the mechanism of interactions between membrane-bound fatty acids and their binding protein: A model system to investigate the behavior of lipid acyl chains in contact with proteins 膜结合脂肪酸及其结合蛋白之间相互作用机制的实验和理论研究:研究脂质酰基链与蛋白质接触行为的模型系统
IF 3.4 3区 生物学 Q1 Chemistry Pub Date : 2022-09-01 DOI: 10.1016/j.chemphyslip.2022.105227
Shigeru Sugiyama , Daisuke Matsuoka , Toshiaki Hara , Masashi Sonoyama , Shigeru Matsuoka , Michio Murata

The interaction of proteins with hydrophobic ligands in biological membranes is an important research topic in the life sciences. The hydrophobic nature of ligands, especially their lack of water solubility, often makes it difficult to experimentally investigate their interactions with proteins, thus hampering quantitative evaluation based on thermodynamic parameters. The fatty acid-binding proteins, particularly FABP3, discussed in this review can recognize fatty acids, a primary component of membrane lipids, with high affinity. The precise three-dimensional structure of fatty acids and related ligands bound in FABP3 and their interaction with the binding pocket will contribute to the understanding of accurately determining physicochemical factors that cause the expression of affinity between protein surfaces and lipids in biological membranes. During the research of FABP3, we encountered many of the problems that were widely implicated in experiments dealing with hydrophobic ligands. To address these issues, we developed experimental methodologies using X-ray crystallography, calorimetry, and surface plasmon resonance. Using these methods and computational approaches, we have obtained several insights into the interaction of hydrophobic ligands with protein binding sites. Structural and functional studies of FABP potentially lead to a better understanding of the interaction between lipids and proteins, and thus, this protein may provide one of the model systems for investigating substance transport across cell membranes and inner membrane systems.

生物膜中蛋白质与疏水配体的相互作用是生命科学领域的一个重要研究课题。由于配体的疏水性,尤其是它们缺乏水溶性,因此很难通过实验研究它们与蛋白质的相互作用,从而阻碍了基于热力学参数的定量评价。本文讨论的脂肪酸结合蛋白,特别是FABP3,可以识别膜脂的主要成分脂肪酸,具有很高的亲和力。结合在FABP3上的脂肪酸和相关配体的精确三维结构及其与结合袋的相互作用将有助于准确确定导致生物膜中蛋白质表面与脂质亲和性表达的理化因素。在FABP3的研究过程中,我们遇到了许多在疏水配体实验中广泛涉及的问题。为了解决这些问题,我们开发了使用x射线晶体学、量热法和表面等离子体共振的实验方法。利用这些方法和计算方法,我们对疏水配体与蛋白质结合位点的相互作用有了一些了解。FABP的结构和功能研究可能有助于更好地理解脂质与蛋白质之间的相互作用,因此,该蛋白可能为研究物质跨细胞膜和内膜系统的转运提供一个模型系统。
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引用次数: 1
Evaluation of liver specific ionizable lipid nanocarrier in the delivery of siRNA 肝特异性电离脂质纳米载体在siRNA递送中的评价
IF 3.4 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-08-01 DOI: 10.1016/j.chemphyslip.2022.105207
Shilpa Rana , Archana Bhatnagar , Suman Singh , Nirmal Prabhakar

Hepcidin, a key regulator of iron homeostasis, has been implicated in the pathogenesis of various iron-related diseases. Although small interfering RNA (siRNA) are potent to modulate the expression of hepcidin, their bioavailability remains a major issue. The β-galactopyranoside-conjugated liposomes (GAL-liposome) targeting liver synthesized hepcidin were prepared by thin lipid film hydration method to encapsulate siRNA and the conjugation of β-galactopyranoside to the lipid nanocarrier was achieved by covalent chemistry. The prepared siRNA loaded GAL-lip were spherical with around 50 nm radius in size as observed by HR-TEM. The zeta potential and polydispersity index of the prepared liposomes were − 19.9 ± 0.96 mV and 0.44 ± 0.05, respectively. The encapsulation efficiency as determined by dialysis bag method was around 91.76 ± 1.74%. The cell viability and cellular uptake analysis was examined in HepG2 cells by MTT assay and flow cytometry, respectively. The stability and cumulative release of siRNA was also assessed. The hepcidin mRNA expression on administration of siRNA loaded GAL-lip was determined in HepG2 cells and in lipopolysaccharide-induced mice model followed by examining itsin vivo biodistribution by fluorescence microscopy. The results suggested thatsiRNA loaded GAL-lip reduced the hepcidin levels, thus, highlighting a novel ligand conjugated ionizable lipid-based nanocarrier for inducing RNA interference.

Hepcidin是铁稳态的关键调节因子,与多种铁相关疾病的发病机制有关。尽管小干扰RNA (siRNA)可以有效地调节hepcidin的表达,但它们的生物利用度仍然是一个主要问题。采用脂膜水合法制备靶向肝合成hepcidin的β-半乳糖苷偶联脂质体(GAL-liposome)包封siRNA,通过共价化学将β-半乳糖苷偶联到脂质纳米载体上。通过透射电镜观察,所制备的siRNA负载GAL-lip为球形,半径约为50 nm。所得脂质体的zeta电位为- 19.9±0.96 mV,多分散性指数为0.44±0.05。透析袋法包封率为91.76±1.74%。用MTT法和流式细胞术检测HepG2细胞的细胞活力和细胞摄取。并对siRNA的稳定性和累积释放进行了评估。在HepG2细胞和脂多糖诱导小鼠模型中测定siRNA负载GAL-lip对hepcidin mRNA表达的影响,并通过荧光显微镜观察其在体内的生物分布。结果表明,sirna负载GAL-lip降低了hepcidin水平,从而突出了一种新的配体共轭可电离脂质纳米载体诱导RNA干扰。
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引用次数: 1
Electrostatic interactions between cationic dendrimers and anionic model biomembrane 阳离子树状大分子与阴离子模型生物膜之间的静电相互作用
IF 3.4 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-08-01 DOI: 10.1016/j.chemphyslip.2022.105214
Khawla Qamhieh , Tommy Nylander

The electrostatic interactions between cationic poly(amidoamine) (PAMAM) dendrimers of different generations, G3, G4, and G6, with net anionic model biomembranes have been predicted by adopting an analytical model based on two dissimilar soft spheres. The influence of bilayer surface charge density, ionic strength, pH, temperature, membrane softness (modeled as changes in bilayer thickness), and dendrimer generation on the attractive interaction was investigated. The attraction was found to decrease with increasing salt concentration, dendrimer charge, and thickness (or softness) of the membrane. On the other hand, the attraction increased with the surface charge density of the membrane, and the size of dendrimer generation. In fact, the attraction was found to be much larger for large generations, like G6 dendrimer that have a higher charge, than it is with small ones like G3 and G4 dendrimers. These results have implications for the use of PAMAM dendrimers as potential gene transfection vectors.

采用基于两种不同软球的分析模型,预测了G3、G4和G6代阳离子型聚氨基胺(PAMAM)树状大分子与净阴离子型生物膜之间的静电相互作用。研究了双层表面电荷密度、离子强度、pH、温度、膜柔软度(以双层厚度变化为模型)和树突分子生成对吸引相互作用的影响。随着盐浓度的增加、树突分子电荷的增加和膜的厚度(或柔软度)的增加,这种吸引力减小。另一方面,随着膜的表面电荷密度和树突状分子生成的大小,膜的吸引力增加。事实上,这种吸引力被发现在大世代中要大得多,比如具有更高电荷的G6树状大分子,而在小世代中,比如G3和G4树状大分子。这些结果对利用PAMAM树突状分子作为潜在的基因转染载体具有启示意义。
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引用次数: 1
Influence of ceramide on lipid domain stability studied with small-angle neutron scattering: The role of acyl chain length and unsaturation 用小角中子散射研究神经酰胺对脂质结构域稳定性的影响:酰基链长和不饱和的作用
IF 3.4 3区 生物学 Q1 Chemistry Pub Date : 2022-07-01 DOI: 10.1016/j.chemphyslip.2022.105205
Mitchell DiPasquale , Tye G. Deering , Dhimant Desai , Arun K. Sharma , Shantu Amin , Todd E. Fox , Mark Kester , John Katsaras , Drew Marquardt , Frederick A. Heberle

Ceramides and diacylglycerols are groups of lipids capable of nucleating and stabilizing ordered lipid domains, structures that have been implicated in a range of biological processes. Previous studies have used fluorescence reporter molecules to explore the influence of ceramide acyl chain structure on sphingolipid-rich ordered phases. Here, we use small-angle neutron scattering (SANS) to examine the ability of ceramides and diacylglycerols to promote lipid domain formation in the well-characterized domain-forming mixture DPPC/DOPC/cholesterol. SANS is a powerful, probe-free technique for interrogating membrane heterogeneity, as it is differentially sensitive to hydrogen’s stable isotopes protium and deuterium. Specifically, neutron contrast is generated through selective deuteration of lipid species, thus enabling the detection of nanoscopic domains enriched in deuterated saturated lipids dispersed in a matrix of protiated unsaturated lipids. Using large unilamellar vesicles, we found that upon replacing 10 mol% DPPC with either C16:0 or C18:0 ceramide, or 16:0 diacylglycerol (dag), lipid domains persisted to higher temperatures. However, when DPPC was replaced with short chain (C6:0 or C12:0) or very long chain (C24:0) ceramides, or ceramides with unsaturated acyl chains of any length (C6:1(3), C6:1(5), C18:1, and C24:1), as well as C18:1-dag, lipid domains were destabilized, melting at lower temperatures than those in the DPPC/DOPC/cholesterol system. These results show how ceramide acyl chain length and unsaturation influence lipid domains and have implications for how cell membranes might modify their function through the generation of different ceramide species.

神经酰胺和二酰基甘油是一类能够成核和稳定有序脂质结构域的脂质,这些结构与一系列生物过程有关。以往的研究利用荧光报告分子探索神经酰胺酰基链结构对富鞘脂有序相的影响。在这里,我们使用小角中子散射(SANS)来研究神经酰胺和二酰基甘油促进结构域形成的能力,这些结构域形成的结构域混合物DPPC/DOPC/胆固醇。SANS是一种强大的、无探针的技术,用于询问膜的非均质性,因为它对氢的稳定同位素质子和氘有不同的敏感性。具体来说,中子对比是通过脂质的选择性氘化产生的,从而能够检测分散在质子化不饱和脂质的基质中富集的氘化饱和脂质的纳米级结构域。使用大的单层囊泡,我们发现用C16:0或C18:0神经酰胺或16:0二酰基甘油(dag)取代10 mol%的DPPC后,脂质结构域持续到更高的温度。然而,当DPPC被短链(C6:0或C12:0)或超长链(C24:0)神经酰胺,或具有任何长度的不饱和酰基链的神经酰胺(C6:1(3), C6:1(5), C18:1和C24:1)以及C18:1- day取代时,脂质结构域被破坏,在比DPPC/DOPC/胆固醇系统更低的温度下熔化。这些结果显示了神经酰胺酰基链长度和不饱和如何影响脂质结构域,并暗示了细胞膜如何通过产生不同的神经酰胺物种来改变其功能。
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引用次数: 5
Doxorubicin delivery systems with an acetylacetone-based block in cholesterol-terminated copolymers: Diverse activity against estrogen-dependent and estrogen-independent breast cancer cells 阿霉素输送系统与乙酰丙酮为基础阻断胆固醇端共聚物:对雌激素依赖性和雌激素非依赖性乳腺癌细胞的不同活性
IF 3.4 3区 生物学 Q1 Chemistry Pub Date : 2022-07-01 DOI: 10.1016/j.chemphyslip.2022.105194
Paweł Misiak , Katarzyna Niemirowicz-Laskowska , Iwona Misztalewska-Turkowicz , Karolina H. Markiewicz , Przemysław Wielgat , Halina Car , Agnieszka Z. Wilczewska

The study presents the synthesis of original cholesterol-terminated copolymers comprising acetylacetone-based (AcacI) and N-isopropylacrylamide (NIPAAm) units with a varied arrangement (block and random copolymers). The nanoprecipitation method was used to form empty and doxorubicin-loaded polymeric nanoparticles (PNPs) from these copolymers, which were further studied in terms of their physicochemical and biological properties. Unexpectedly, it was revealed that even empty PNPs are effective against breast cancer cells, specifically towards estrogen-dependent MCF-7 cell line. The anti-cancer efficacy was further improved when a low dose of doxorubicin was introduced to the tested systems. It was shown that the proposed carriers modulate doxorubicin (DOX) compatibility with representatives of normal cells, including immune cells, cardiomyocyte cells, and fibroblasts, and reduce side effects associated with standard chemotherapy. The use of these carriers might be a strategy leading to enhancement of DOX activity in cancer cells which develop resistance through decreased drug penetration or drug efflux.

本研究提出了由乙酰丙酮基(AcacI)和n -异丙基丙烯酰胺(NIPAAm)单元组成的原始胆固醇端共聚物的合成,这些共聚物具有不同的排列(嵌段和无规则共聚物)。采用纳米沉淀法将这些共聚物制备成空的和负载阿霉素的聚合物纳米颗粒(PNPs),并进一步研究了它们的物理化学和生物学性质。出乎意料的是,即使是空的PNPs也对乳腺癌细胞有效,特别是对雌激素依赖性MCF-7细胞系。当低剂量的阿霉素被引入测试系统时,抗癌效果进一步提高。研究表明,拟议的载体调节了阿霉素(DOX)与正常细胞的相容性,包括免疫细胞、心肌细胞和成纤维细胞,并减少了与标准化疗相关的副作用。使用这些载体可能是一种通过减少药物渗透或药物外排而产生耐药性的癌细胞中DOX活性增强的策略。
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引用次数: 2
期刊
Chemistry and Physics of Lipids
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