1182-65-6Relevant academic research and scientific papers
Liposomes actively recognizing the glucose transporter GLUT1 and integrin αvβ3 for dual-targeting of glioma
Fu, Qiuyi,Zhao, Yi,Yang, Zhongzhen,Yue, Qiming,Xiao, Wenjiao,Chen, Yang,Yang, Yang,Guo, Li,Wu, Yong
, (2019)
The treatment of glioma is a great challenge because of the existence of the blood–brain barrier (BBB). In order to develop an efficient glioma-targeting drug delivery system to greatly improve the brain permeability of anti-cancer drugs and target glioma, a novel glioma-targeted glucose-RGD (Glu-RGD) derivative was designed and synthesized as ligand for preparing liposomes to effectively deliver paclitaxel (PTX) to cross the BBB and target glioma. The liposomes were prepared and characterized for particle size, zeta potential, encapsulation efficiency, release profile, stability, hemolysis, and cell cytotoxicity. Also, the Glu-RGD modified liposomes showed superior targeting ability in in vitro and in vivo evaluation as compared to naked PTX, non-coated, singly modified liposomes and liposomes co-modified by physical blending. The relative uptake efficiency and concentration efficiency were enhanced by 4.41- and 4.72-fold compared to that of naked PTX, respectively. What is more, the Glu-RGD modified liposomes also displayed the maximum accumulation of DiD-loaded liposomes at tumor sites compared to the other groups in in vivo imaging. All the results in vitro and in vivo suggested that Glu-RGD-Lip would be a potential delivery system for PTX to treat integrin αvβ3-overexpressing tumor-bearing mice.
Self-organization of cholesterol-side-chain liquid crystalline polymers by tailoring the main chain structure and flexible spacer length
Yang, Xiwen,Chen, Shaonan,Luo, Hang,Xu, Haoran,Chen, Sheng
, p. 5429 - 5440 (2019)
Three kinds of side-chain liquid crystalline polymers (SCLCPs), in which cholesteryl mesogens (Chol) were linked to polyacrylate (PCholAC-m), polymethacrylate (PCholMC-m), and poly(2-vinylbenzene-1,4-dioate) (PCholVA-m) backbones through methylene spacers of different lengths (m = 0, 2, 4, 6, 8, and 10), were successfully synthesized using free-radical polymerization. The phase behavior and structure of the polymers were investigated in detail using DSC, POM, and SAXS. The results indicated that the Chol-SCLCPs displayed interesting self-organization by varying the main-chain structure and spacer length. The polymers initially form a smectic A phase, except for PCholAC-0 without a liquid crystalline phase. Next, polymers PCholAC-m (m = 2, 4, 6) formed a two-layer smectic A phase in which the alkyl tail was overlapped (SmA2). Two-phase coexisting structures were observed in PCholAC-m (m = 8, 10), including a bilayer smectic A phase in which the alkyl tail was inserted into the mesogens (SmAd) and a single-layer smectic A phase in which the mesogens were overlapped (SmA1). Similar results were observed for PCholMC-m. Furthermore, PCholMC-0 possessed a stable bilayer SmA2 owing to the methyl steric effect of the main chain. PCholVA-m (m = 0, 2, 4) samples showed a well-defined smectic A phase in which the backbone was squeezed by the parallel side chains on both sides. PCholVA-6 and PCholVA-10 exhibited a SmAd phase. The two-phase coexisting structures were also found in PCholVA-8. Finally, the glass transition temperature of the polymers decreased with increasing flexible spacer length because the flexible spacer acted as an internal plasticizer in the system. However, changes in the polymer clearing points demonstrated the diversity resulting from the different smectic A phase structures.
The synthesis of cholesterol-based cationic lipids with trimethylamine head and the effect of spacer structures on transfection efficiency
Kim, Bieong-Kil,Bae, Yun-Ui,Doh, Kyung-Oh,Hwang, Guen-Bae,Lee, Sung-Hye,Kang, Hyungu,Seu, Young-Bae
, p. 3734 - 3737 (2011)
Five cholesterol-based cationic lipids were newly synthesized based on cholest-5-en-3β-oxyethane-N,N,N-trimethylammonium bromide (Chol-ETA) structure where the cholesterol backbone is linked to cationic head via various lengths of ether-linked carbon spacer. The transfection efficiency of these compounds was increased in order of three (Chol-PRO) four (Chol-BTA) two (Chol-ETA) methylene unit in their spacer, and was decreased by an addition of isomethyl group to Chol-PRO spacer. In case of the presence of multiple bonds in the spacer, it required the more cationic lipids in liposome formulation than single bond in the spacer to present similar transfection efficiency. Crown Copyright
Synergistic targeted delivery of payload into tumor cells by dual-ligand liposomes co-modified with cholesterol anchored transferrin and TAT
Tang, Jie,Zhang, Li,Liu, Yayuan,Zhang, Qianyu,Qin, Yao,Yin, Yujia,Yuan, Wenmin,Yang, Yuting,Xie, Yafei,Zhang, Zhirong,He, Qin
, p. 31 - 40 (2013)
This study was mainly focused on developing a dual-ligand liposomal delivery system to enhance both targeting specificity and cellular uptake. The specific ligand transferrin (TF) and the cationic cell-penetrating peptide TAT were connected with cholesterol via a polyethylene glycol (PEG) spacer to prepare the dualligand liposomes (TAT/TF-PEG-LP). Then the in vitro cellular uptake by three kinds of cells that possessed different expressing levels of transferrin receptor (TFR) and the in vivo delivery efficiency were evaluated. Compared to the single-ligand TAT or TF modified liposomes (TAT-PEG-LP or TF-PEG-LP), TAT/TF-PEG-LP exhibited the enhanced cellular uptake and selectivity via the synergistic effect of both ligands in vitro. The ex vivo fluorescence imaging of tumors, the qualitative observation of tumor frozen section and the quantitative determination of cellular uptake in tumor tissues altogether showed the in vivo delivery efficiency of TAT/TF-PEG-LP was higher than that of other liposomes. In conclusion, the dual-ligand liposomes co-modified with TF and TAT possessed a strong capability for synergistic targeted delivery of payload into tumor cells both in vitro and in vivo.
Efficacious Doxorubicin Delivery Using Glutathione-Responsive Hollow Non-phospholipid Vesicles Bearing Lipoyl Cholesterols
Kumar, Krishan,Yadav, Lalit,Kondaiah, Paturu,Chaudhary, Sandeep
, p. 1633 - 1640 (2019)
In this study, we developed redox-sensitive vesicles using synthesised lipoyl cholesterol derivatives, a non-ionic surfactant and an optimum level of free cholesterol. Interestingly, concentration-dependent self-assembly was observed by scanning electron microscopy, wherein vesicles manifested as hollow spherical (at 0.15 mm) and triangular (0.50 mm). The redoxresponsive characteristics of the vesicles was probed in the presence of dithiothreitol; they underwent a clear increase in size as observed by dynamic light scattering measurements. These vesicles could easily encapsulate an anticancer drug, doxorubicin, and were observed to be stable in the presence of serum. They showed substantial release of the drug in response to biologically relevant stimulus, that is, glutathione. A toxicity assessment on HeLa and HepG2 cancer cells demonstrated activities of the drug-loaded vesicles comparable to that of free drug, whereas significantly enhanced toxicity and apoptotic induction were observed against drug-resistant HeLa cells, which was determined by studying the cellular internalisation of doxorubicin.
Synthesis of photoresponsive cholesterol-based azobenzene organogels: Dependence on different spacer lengths
Ren, Yuchun,Wang, Bin,Zhang, Xiuqing
, p. 1089 - 1095 (2015)
A series of azobenzene-cholesterol organogel compounds (M0 -M12 ) with different spacers were designed and synthesized. The molecular structures were confirmed by 1H NMR and 13C NMR spectroscopy. The rapid and reversible photoresponsive properties of the compounds were investigated by UV-vis spectroscopy. Their thermal phase behaviors were studied by DSC. The length of the spacer plays a crucial role in the gelation. Compound M6 is the only one that can gelate in ethanol, isopropanol and 1-butanol and the reversible gel-sol transitions are also investigated. To obtain visual insight into the microstructure of the gels, the typical structures of the xerogels were studied by SEM. Morphologies of the aggregates change from flower-like, network and rod with different sizes. By using IR and XRD characterization, it is found that intermolecular H-bonding, the solvents and van der Waals interaction are the main contributions to the specific superstructure.
Identification and characterization of β-sitosterol target proteins
Lomenick, Brett,Shi, Heping,Huang, Jing,Chen, Chuo
, p. 4976 - 4979 (2015)
β-Sitosterol is the most abundant plant sterol in the human diet. It is also the major component of several traditional medicines, including saw palmetto and devil's claw. Although β-sitosterol is effective against enlarged prostate in human clinical trials and has anti-cancer and anti-inflammatory activities, the mechanisms of action are poorly understood. Here, we report the identification of two new binding proteins for β-sitosterol that may underlie its beneficial effects.
Synthesis and characterization of new chiral liquid crystal monomers containing steroid unit
Chen, Qifan,Liu, Xiaofeng,Guo, Zhihao,Xu, Xiaoxu,Lu, Yanhua
, p. 1 - 11 (2018)
To reduce the bulky steric hindrance, improve the reactivity of diosgenin and cholesterol, and obtain mesophase of their derivatives, the commercially available cholesterol and diosgenin were allowed to be structurally modified. Four new chiral LC intermediate compounds (c～f) and the corresponding monomers (M1?M4) with different longer spacer were synthesized. The chemical structures, optical texture, thermal behavior and mesophase structure of all the mesogenic compounds obtained in this study were characterized by FT-IR, 1H-NMR, polarizing optical microscopy, differential scanning calorimetry, and X-ray diffraction measurements. The experimental results showed that the intermediate compounds containing diosgenyl groups c and d only showed a mesophase and exhibited fan-shaped texture of a smectic A (SA) phase, while the compounds containing terminal cholesteryl groups e and f showed two mesophases and exhibited fan-shaped texture of a SA phase, and oily streak texture and focal conic texture of cholesteric phase, respectively. The four chiral monomers M1?M4 all revealed cholesteric oily streak texture and focal conic texture. In addition, the melting temperature (Tm) and isotropic temperature (Ti) of the mesogenic compounds decreased with increasing the flexible spacer length. Compared with the intermediate compounds or monomers based on cholesterol, the compounds or monomers based on diosgenin showed higher Tm and Ti.
Differential response of cholesterol based pyrimidine systems with oxyethylene type spacers to gelation and mesogen formation in the presence of alkali metal ions
Datta, Sougata,Bhattacharya, Santanu
, p. 1945 - 1953 (2015)
A new series of lipophilic cholesteryl derivatives of 2,4,6-trichloro-pyrimidine-5-carbaldehyde has been synthesized. Oxyethylene spacers of variable lengths were inserted between the hydrogen bonding promoting pyrimidine core and the cholesteryl tail in order to understand their effect on the self-assembly of these compounds. Only compound 1a with the shortest spacer formed a gel in organic solvents such as n-butanol and n-dodecane. While other members (1b and c) having longer spacers led to sol formation and precipitation in n-butanol and n-dodecane respectively. The self-assembly phenomena associated with the gelation process were investigated using temperature-dependent UV-Vis and CD-spectroscopy. The morphological features of the freeze-dried gels obtained from different organic solvents were examined by scanning electron microscopy (SEM) and atomic force microscopy (AFM). The solid phase behaviours of these molecules and their associated alkali metal ion complexes were explored using polarized optical microscopy (POM) and differential scanning calorimetry (DSC). The molecular arrangements in the xerogel and in the solid state were further probed using a wide-angle X-ray diffraction (WAXD) technique. Analysis of the wide-angle X-ray diffraction data reveals that this class of molecules adopts a hexagonal columnar organization in the gel and in the solid state. Each slice of these hexagonal columnar structures is composed of a dimeric molecular-assembly as a building block. Significant changes in the conformation of the oxyethylene chains could be triggered via the coordination of selected alkali metal ions. This led to the production of interesting metal ion promoted mesogenic behaviour.
Liquid crystals derived from hydrogen-bonded supramolecular complexes of pyridinylated hyperbranched polyglycerol and cholesterol-based carboxylic acids
Felekis, Theodores,Tziveleka, Leto,Tsiourvas, Dimitris,Paleos, Constantinos M.
, p. 1705 - 1710 (2005)
A hyperbranched polyether polyol was reacted with isonicotinoyl chloride hydrochloride for the introduction of the pyridinyl moiety at the external surface. This pyridinylated hyperbranched polymer was subsequently interacted with cholesterol-based carboxylic acids for the formation of the corresponding hydrogen-bonded supramolecular complexes. The materials obtained exhibited smectic A liquid crystalline phases over a broad thermal range from room temperature up to above 170°C. Within this smectic layer the cholesterol moieties are located above and below the hyperbranched scaffold. Increasing the spacer length, located between the carboxylic group and the cholesterol moiety, the temperature range of the liquid crystalline phases of the complexes is lowered.
