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11.
An amphiphilic prodrug of anti-HIV nucleoside analogue, cholesteryl-phosphonyl zidovudine (CPNZ) was synthesized. An aqueous suspension containing CPNZ self-assemblies was obtained through injecting the ethanol solution of CPNZ and cholesteryl succinyl poly(ethylene glycol) 1500 (20:1, mol/mol) into water under agitation. Hydrophobic interaction may be the driving force of molecular self-assembly. The self-assemblies were nanoscale with ∼100 nm in size, and remained stable for a long time. Degradation of CPNZ self-assemblies was investigated in various environments including buffered solutions, plasma and rabbit tissue homogenates. CPNZ was degraded very slowly in neutral solutions but rapidly in various plasma with the half-lives (t1/2) of less than 20 h. Tissue homogenates degraded CPNZ with varied rates depending on enzyme activity. CPNZ self-assemblies showed potent anti-HIV activity on MT4 cell model, the anti-HIV 50% effective concentration (EC50) of which was 1 nM, only equal to 1/5 of AZT EC50. CPNZ was rapidly eliminated from circulation and distributed into the mononuclear phagocyte system (MPS) including liver, spleen and lung after bolus intravenous administration of CPNZ self-assemblies followed slowly elimination. The possible products include AZT-5′-H-phosphonate, AZT and their derivatives. The MPS-targeted effect and high anti-HIV activity of CPNZ self-assemblies make them become a promising self-assembled drug delivery system (SADDS).  相似文献   
12.
The interactions between three different protein antigens and dioctadecyldimethylammonium bromide (DODAB) dispersed in aqueous solutions from probe sonication or adsorbed as one bilayer onto particles was comparatively investigated. The three model proteins were bovine serum albumin (BSA), purified 18 kDa/14 kDa antigens from Taenia crassiceps (18/14-Tcra) and a recombinant, heat-shock protein hsp-18 kDa from Mycobacterium leprae. Protein-DODAB complexes in water solution were characterized by dynamic light scattering for sizing and zeta-potential analysis. Cationic complexes (80–100 nm of mean hydrodynamic diameter) displayed sizes similar to those of DODAB bilayer fragments (BF) in aqueous solution and good colloid stability over a range of DODAB and protein concentrations. The amount of cationic lipid required for attaining zero of zeta-potential at a given protein amount depended on protein nature being smaller for 18 kDa/14 kDa antigens than for BSA. Mean diameters for DODAB/protein complexes increased, whereas zeta-potentials decreased with NaCl or protein concentration. In mice, weak IgG production but significant cellular immune responses were induced by the complexes in comparison to antigens alone or carried by aluminum hydroxide as shown from IgG in serum determined by ELISA, delayed type hypersensitivity reaction from footpad swelling tests and cytokines analysis. The novel cationic adjuvant/protein complexes revealed good colloid stability and potential for vaccine design at a reduced DODAB concentration.  相似文献   
13.
Self-assembled monolayers of a β-cyclodextrin with methyl sulfides on the primary sites of the molecule and mono-functionalized with anthraquinone on a secondary site have been formed on gold electrodes. The surface coverages obtained by electrochemistry are consistent with values reported previously or calculated for similar non-electroactive β-CD derivatives. The electron transfer rate constants vary markedly with pH, increasing rapidly between pH 7 and 9 to values of approximately 700–900 s?1. These values are faster than reported previously for thiol derivatives of anthraquinone dispersed in an alkylthiol SAM matrix. Near pH 6, slow electron transfer is observed with a splitting into individual one-electron steps. Lowering the pH further results in very sluggish kinetics and indistinguishable peaks. Inclusion of naphthalene into the β-CD cavity appears to affect the anodic rate constant, and a small potential shift occurs. The efficient electron transfer of the anthraquinone spaced from the gold surface by a β-CD unit suggests promise for use of such molecules as ‘immobilized artificial enzymes’.  相似文献   
14.
目的设计合成含IKVAV的两亲性肽,探讨其体外自组装成三维多孔凝胶及体内诱导血管生成的可行性。方法固相法合成肽.自组装成凝胶,TEM观察凝胶结构。实验组:配制1wt%的肽溶液,pH值为9.0;对照组:配制16.67%的明胶,DH值为7.4。各取1mL,分别注射于大鼠脊柱两侧皮下,术后1周观察全身反应及局部皮肤。2周后取材,固定,常规HE染色及VEGF免疫组织化学染色。结果高效液相频谱仪及质谱仪示肽纯度及分子量分别为95.22%与1438,TEM示凝胶为交织成网状的纳米纤维。术后1周动物存活良好,无全身不良反应,局部皮肤无红肿、无坏死。实验组:1wt%的肽体内自组装成凝胶,血管长入凝胶内部,管腔内可发现红细胞;术后2周,VEGF阳性。对照组:明胶内未发现血管,VEGF阴性。结论本实验合成含IKVAV两亲性肽,在PBS溶液中可自组装成凝胶且体内可诱导新生血管生成。  相似文献   
15.
DNA Self-assembly for Nanomedicine   总被引:1,自引:0,他引:1  
Self-assembling DNA nanostructures based on rationally designed DNA branch junction molecules has recently led to the construction of patterned supramolecular structures with increased complexities. An intrinsic value of DNA tiles and patterns lies in their utility as molecular pegboard for deterministic positioning of molecules or particles with accurate distance and architectural control. This review will discuss the state-of-art developments in self-assembled DNA nanostructural system. Biomedical aspects of information guided DNA nanostructures will also be summarized. We illustrate both the use of simple DNA artworks for sensing, computation, drug delivery and the application of more complex DNA architectures as scaffolds for the construction of protein and nanoparticle arrays.  相似文献   
16.
《药学学报(英文版)》2023,13(2):879-896
Immunotherapy combined with effective therapeutics such as chemotherapy and photodynamic therapy have been shown to be a successful strategy to activate anti-tumor immune responses for improved anticancer treatment. However, developing multifunctional biodegradable, biocompatible, low-toxic but highly efficient, and clinically available transformed nano-immunostimulants remains a challenge and is in great demand. Herein, we report and design of a novel carrier-free photo-chemotherapeutic nano-prodrug COS-BA/Ce6 NPs by combining three multifunctional components—a self-assembled natural small molecule betulinic acid (BA), a water-soluble chitosan oligosaccharide (COS), and a low toxic photosensitizer chlorin e6 (Ce6)—to augment the antitumor efficacy of the immune adjuvant anti-PD-L1-mediated cancer immunotherapy. We show that the designed nanodrugs harbored a smart and distinctive “dormancy” characteristic in chemotherapeutic effect with desired lower cytotoxicity, and multiple favorable therapeutic features including improved 1O2 generation induced by the reduced energy gap of Ce6, pH-responsiveness, good biodegradability, and biocompatibility, ensuring a highly efficient, synergistic photochemotherapy. Moreover, when combined with anti-PD-L1 therapy, both nano-coassembly based chemotherapy and chemotherapy/photodynamic therapy (PDT) could effectively activate antitumor immunity when treating primary or distant tumors, opening up potentially attractive possibilities for clinical immunotherapy.  相似文献   
17.
A new method for the formation of xanthic acids H(CH2)nCS2H (n=8, 10, 12) in a non-polar solvent from the corresponding potassium salts was developed. It was found that the xanthic acids spontaneously adsorb onto gold electrodes, via a mechanism that is proposed to be similar to the adsorption of thiols on gold surfaces. The xanthate modified gold electrodes were studied by cyclic voltammetry. It was found that the xanthate layers efficiently block the current from a ferro/ferri redox couple in aqueous solution. Studies of the electrochemical desorption of the xanthate layer supported the fact that xanthic acids spontaneously form a self-assembled monolayer on the electrode.  相似文献   
18.
Studies on the adsorption of oppositely charged colloidal particles ultimately resulted in multilayered polyelectrolyte self-assembly. The inception of layer-by-layer constructed particles facilitated the production of multifunctional, stimuli-responsive carrier systems. An array of synthetic and natural polyelectrolytes, metal oxides and clay nanoparticles is available for the construction of multilayered nanocoats on a multitude of substrates or removable cores. Numerous substrates can be encapsulated utilizing this technique including dyes, enzymes, drugs and cells. Furthermore, the outer surface of the particles presents and ideal platform that can be functionalized with targeting molecules or catalysts. Some processing parameters determining the properties of these successive self-assembly constructs are the surface charge density, coating material concentration, rinsing and drying steps, temperature and ionic strength of the medium. Additionally, the simplicity of the layer-by-layer assembly technique and the availability of established characterization methods, render these constructs extremely versatile in applications of sensing, encapsulation and target- and trigger-responsive drug delivery.  相似文献   
19.
目的 利用有机硒催化一氧化氮(No)供体释放NO的能力设计一种新型人工血管支架材料。方法固载有机硒催化剂的聚乙烯亚胺( SePEI)作为聚阳离子,与聚阴离子聚谷氨酸(PGA)在静电纺丝得到的纳米纤维支架聚己内酯(PCL)表面层层自组装,用紫外和原子吸收进行了定性和定量的表征层层自组装结构;在还原型谷胱甘肽(GSH)的存...  相似文献   
20.
本文设计合成了两种光敏的双亲性分子,分别具有单齿和三齿的结构,这两种双亲性分子可自组装成球形和楔形超分子纳米粒。超分子外部带有氨基的PEG片段可以通过静电作用与核酸结合。本文对超分子输送寡聚核苷酸进入细胞的效果进行了评价。结果表明,具有三齿结构的分子与核酸形成的复合物通过内吞作用可以有效地将核酸输送进入细胞,而单齿结构的复合物却几乎不具有此能力。给予光照后,三齿的超分子发生醌甲基化重排而解离,从而释放核酸。  相似文献   
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