Mitochondria‐Targeting,Intracellular Delivery of Native Proteins Using Biodegradable Silica Nanoparticles

Mitochondria are key organelles in mammalian cells whose dysfunction is linked to various diseases. Drugs targeting mitochondrial proteins provide a highly promising strategy for potential therapeutics. Methods for the delivery of small‐molecule drugs to the mitochondria are available, but these are not suitable for macromolecules, such as proteins. Herein, we report the delivery of native proteins and antibodies to the mitochondria using biodegradable silica nanoparticles (BS–NPs). The modification of the nanoparticle surface with triphenylphosphonium (TPP) and cell‐penetrating poly(disulfide)s (CPD) facilitated their rapid intracellular uptake with minimal endolysosomal trapping, providing sufficient time for effective mitochondrial localization followed by glutathione‐triggered biodegradation and of native, functional proteins into the mitochondria.     

Mitochondria‐Targeting,Intracellular Delivery of Native Proteins Using Biodegradable Silica Nanoparticles

Mitochondria are key organelles in mammalian cells whose dysfunction is linked to various diseases. Drugs targeting mitochondrial proteins provide a highly promising strategy for potential therapeutics. Methods for the delivery of small‐molecule drugs to the mitochondria are available, but these are not suitable for macromolecules, such as proteins. Herein, we report the delivery of native proteins and antibodies to the mitochondria using biodegradable silica nanoparticles (BS–NPs). The modification of the nanoparticle surface with triphenylphosphonium (TPP) and cell‐penetrating poly(disulfide)s (CPD) facilitated their rapid intracellular uptake with minimal endolysosomal trapping, providing sufficient time for effective mitochondrial localization followed by glutathione‐triggered biodegradation and of native, functional proteins into the mitochondria.     

A Novel Approach to High Performance Elastomer by Using Clay

Summary: A novel method was developed to prepare an exfoliated styrene butadiene rubber (SBR)/clay nanocomposite with a strong interface between the clay layers and the rubber. An exfoliation mechanism was proposed and verified based on X‐ray diffraction (XRD)/transmission electron microscopy (TEM) analyses of the intercalation/exfoliation phenomena after each step of the process. The significant improvements of mechanical properties may give the first evidence that both exfoliation and a strong interface play critical roles in nanoreinforcement.

TEM image of a SBR/AA‐clay nanocomposite.     

A General Strategy for Targeting Drugs to Bone

Targeting drugs to their desired site of action can increase their safety and efficacy. Bisphosphonates are prototypical examples of drugs targeted to bone. However, bisphosphonate bone affinity is often considered too strong and cannot be significantly modulated without losing activity on the enzymatic target, farnesyl pyrophosphate synthase (FPPS). Furthermore, bisphosphonate bone affinity comes at the expense of very low and variable oral bioavailability. FPPS inhibitors were developed with a monophosphonate as a bone‐affinity tag that confers moderate affinity to bone, which can furthermore be tuned to the desired level, and the relationship between structure and bone affinity was evaluated by using an NMR‐based bone‐binding assay. The concept of targeting drugs to bone with moderate affinity, while retaining oral bioavailability, has broad application to a variety of other bone‐targeted drugs.     

Novel Green Route of Synthesis of ZnO Nanoparticles by Using Natural Biodegradable Polymer and Its Application as a Catalyst for Oxidation of Aldehydes

ZnO nanoparticles have been synthesized by using biodegradable natural biopolymer viz. Gum Tragacanth. This single step approach is very cost effective and reproducible. The reaction time and concentration of precursor zinc acetate play a major role in the nature and growth of ZnO nanoparticles. ZnO nanoparticles were characterized by X-ray diffraction, SEM, FTIR, EDAX, UV-visible spectroscopy and TEM. ZnO nanoparticles with 20-30 nm in diameter and hexagonal morphology were found; dispersed uniformly. Raman spectrum shows the mode E₂ high at 437 cm^?1 that is related to the vibration of wurtzite Zn-O bond in crystal structure of ZnO. The space between adjacent lattice fringes is ～ sharp 2.42 Å. UV-visible absorption spectrum shows the sharp absorption band at 308 nm assigned to the intrinsic transition from valance band to conduction band. The ZnO nanoparticles display superior catalytic activity of conversion of aldehyde to acid as compared to bulk-ZnO material, because of high surface area of ZnO nanoparticles. A trace amount of ZnO nanoparticles catalyst required for organic conversion. The ZnO nanoparticles as catalyst are highly stable, recyclable and efficient in its activity.     

一种通过纳米粒子的组装制备基于二氧化铈中孔材料的简易方法

用HF或者HCl作联合剂,三嵌段共聚物表面活性剂作模板剂,通过二氧化铈纳米粒子(或者过渡金属掺杂的二氧化铈纳米粒子)组装形成具有热稳定和晶化孔壁的基于二氧化铈的中孔材料。焙烧该合成的超分子模板中孔结构的材料可以形成具有高比表面的基于二氧化铈的中孔材料,这些中孔材料用不同的光谱技术表征。通过D₂-OH交换测得的二氧化铈表面的羟基在组装过程和中孔材料的稳定性方面至关重要。联结剂中的卤素离子(F和Cl离子)可以替代中孔材料的表面羟基,从而影响这些中孔材料的结构稳定性和光学活性,而用具有3 d的过渡金属在组装前掺杂二氧化铈纳米粒子可以显著地提高中孔材料的光学活性,这种提高主要归结为通过掺杂可以促使能量转移的提高。     

一种制备镍纳米颗粒的新方法

通过超声照射使2-乙基己酸镍和金属钠在液体石蜡中发生置换反应, 成功地制备了具有六方晶型结构的表面修饰镍纳米颗粒, 并采用多种现代分析手段如TEM、ED、XRD、XPS和TG对所制备的产品进行结构、形貌和热稳定性能的表征. 结果表明, 所制得的镍纳米颗粒粒径较小, 分布范围在7～43 nm之间, 并有着良好的热稳定性能.     

基于金包裹磁性纳米粒子与适配体修饰CdTe纳米探针的凝血酶检测方法

构建了一个适配体修饰的CdTe纳米探针,利用磁性纳米粒子的分离技术,采用示差脉冲伏安法检测凝血酶。磁性纳米粒子作为分离材料,CdTe纳米粒子作为电化学探针,通过凝血酶的特异性识别,适配体从DNA双链中解旋,并与凝血酶结合形成G-四重体结构,达到检测凝血酶的目的,检出限达0.13pmol/L。该方法灵简便、灵敏、成本低,并成功用于实际样品的检测。此外,该方法可被广泛应用于蛋白质监测和疾病诊断。     

A Facile Approach to Well-Dispersible CeO2 Nanoparticles

18 nm CeO₂ with surface being functionalized by nitrate groups were prepared to yield a stable suspension in acidic aqueous solution. Different from the bare ones, these suspensions precipitated rapidly when the solution became basic. Further tuning the solution back to acidic led to a stable suspension again. This phenomenon was explained in terms of the electrostatic repulsion of electrical double layers of intensive surface bound nitrate groups and acidic medium.     

利用磁性可回收的Fe_3O_4纳米颗粒催化剂合成苯并咪唑的新方法(英文)

Magnetically recoverable Fe3O4 nanoparticles have been synthesized as a catalyst for the cyclocondensation of 1,2-phenylenediamines with orthoesters under solvent-free conditions.Catalyst loadings can be as low as 1 mol% to give high yields of the corresponding benzimidazole derivative at 80 °C.This green method offers significant advantages in terms of its simplicity,low catalyst loadings,high product yields,and non-toxic nature.The Fe3O4 nanoparticles were characterized by X-ray diffraction,transmission electron microscopy,and Fourier transform infrared spectroscopy.     

A Novel Approach for Mixing ZnO Nanoparticles into Poly(ethyl methacrylate)

A novel and versatile approach for the mixing of ZnO nanofillers into a host polymer matrix, poly(ethyl methacrylate) (PEMA), is reported. Firstly, ZnO nanoparticles are deposited onto the surface of polystyrene (PS) colloidal particles in a “raspberry‐like” fashion and subsequently obtained PS/ZnO composite particles are mixed into the PEMA matrix in the range of 0.5 to 5 wt.‐%. Microscopic analyses reveal a homogenous distribution of PS/ZnO domains into the PEMA matrix even at 5 wt.‐% loading level. Thermogravimetric analysis and differential scanning calorimetry results indicate an improvement in thermal stability of PEMA matrix after mixing with PS/ZnO filler particles. A significant enhancement in mechanical properties of PEMA matrix in the presence of PS/ZnO particles has been evidenced by dynamic mechanical analysis and three point bending measurements.

     

靶向抑制DNA拓扑异构酶的抗肿瘤药物研究

DNA拓扑异构酶是真核细胞和原核细胞中的一种基本酶,广泛存在于细胞核中,对DNA的转录、复制以及基因表达过程中的DNA拓扑结构的改变起着重要的作用。研究发现DNA拓扑异构酶在肿瘤组织中高度表达,许多抗肿瘤药物的作用机制与抑制拓扑异构酶有关,目前拓扑异构酶已成为筛选抗肿瘤药物的重要靶点。     

Solubility Enhancement of Antidiabetic Drugs Using a Co-Crystallization Approach

The co-crystallization approach has been used to enhance specific desirable properties of active pharmaceutical ingredients (APIs) such as solubility, dissolution rate, and stability. Solubility is a fundamental property that affects the bioavailability and dosage of the API. The co-crystal approach is one of the emerging methods with the potential for improving the solubility of these drugs. This paper reviews the latest progress on improving the solubility of some antidiabetic drug molecules using the co-crystal approach.     

Carbon Black Detector,A Novel Approach to Visible Spectroscopy of Liquids Using Photoacoustic Detection

Abstract

A simple and reproducible method of recording visible spectra of solutions using photoacoustic spectrometry and carbon black as a thermal detector is introduced. Light intensity is proportionally measured by carbon black detector, a microphone system and a simple cell compartment placed after monochromator for liquid samples. Exact match with the absorption spectra is found with certain standard solutions. Aqueous solutions of Cr(III), KMnO₄, disodium fluorescein and chlorpromazine semiquinone cation radicals are tested.     

A One-Pot Approach to Novel Pyridazine C-Nucleosides

The synthesis of glycosides and modified nucleosides represents a wide research field in organic chemistry. The classical methodology is based on coupling reactions between a glycosyl donor and an acceptor. An alternative strategy for new C-nucleosides is used in this approach, which consists of modifying a pre-existent furyl aglycone. This approach is applied to obtain novel pyridazine C-nucleosides starting with 2- and 3-(ribofuranosyl)furans. It is based on singlet oxygen [4+2] cycloaddition followed by reduction and hydrazine cyclization under neutral conditions. The mild three-step one-pot procedure leads stereoselectively to novel pyridazine C-nucleosides of pharmacological interest. The use of acetyls as protecting groups provides an elegant direct route to a deprotected new pyridazine C-nucleoside.     

A Novel Synthetic Approach to Phosphorylated Peptidomimetics

It has been shown that the derivatives of diethyl 5‐amino‐2‐phthalimidoalkyl‐1,3‐oxazol‐4‐ylphosphonates can be employed in the synthesis of phosphorylated peptidomimetics containing the phosphonoglycine residue. The reaction of diethyl 5‐alkylamino‐2‐aminoalkyl‐1,3‐oxazol‐4‐ylphosphonates with unsaturated azlactones was utilized to obtain phosphorylated peptidomimetics with dehydroamino acid moieties. The double bond in the latter was reduced with zinc in acetic acid to provide the corresponding saturated peptidomimetics containing a diethoxyphosphoryl group in the side chain.     

Photoelectrochemical Sensor for Isoniazid: Application in Drugs Used in the Treatment of Tuberculosis

The present work describes the development of a photoelectrochemical sensor based on titanium dioxide, cadmium telluride quantum dots and the tris (2,2′-bipyridyl) ruthenium(II) chloride complex for detection of Isoniazid (INH). The Ru(bpy)₃²⁺/CdTe-QDs/TiO₂/FTO photoelectrochemical platform was characterized by scanning electrochemical microscopy, electrochemical impedance spectroscopy and amperometry. The photoelectrochemical sensor presented two linear ranges for INH concentrations ranging from 0.5 to 150 μmol L⁻¹ and 150 to 1270 μmol L⁻¹, with a theoretical detection limit of 0.02 μmol L⁻¹. The sensor was successfully applied for the determination of INH in drugs samples used in the treatment of tuberculosis.