Starburst pamam dendrimers: Synthetic approaches,surface modifications,and biomedical applications

Dendrimers are having novel three dimensional, synthetic hyperbranched, nano-polymeric structure. Among all of the dendrimers, Poly-amidoamine (PAMAM) dendrimer are used enormously applying materials in supramolecular chemistry. This review described the structure, characteristic, synthesis, toxicity, and surface modification of PAMAM dendrimer. Various strategies in supramolecular chemistry of PAMAM for synthesizing it at commercial and laboratory scales along with their limitations and applications has also discussed. When compared to other nano polymers, the characteristics of supramolecular PAMAM dendrimers in nanopolymer science has shown significant achievement in transporting drugs for molecular targeted therapy, particularly in host–guest reaction. It also finds its applications in gene transfer devices and imaging of biological systems with minimum cytotoxicity. From that viewpoint, this review has elaborated the structural and safety aspect of PAMAM for targeted drug delivery with pharmaceuticals in addition to the biomedical application.     

树状大分子在有机合成中的应用

近20年来树状大分子由于其特殊的结构而引起了科学家们的广泛关注;作为一类新型的高负载量载体应用于有机合成和催化是树状大分子重要的应用领域之一。本文主要介绍树状大分子和树脂固载树状大分子两类载体,重点对它们作为高负载量载体在有机合成和非均相催化反应中的应用研究进行了总结。     

一类新的多分枝大分子

本文介绍了一类新的瀑布状的多分枝大分子(cascade)。这种合成方法可以很精确地控制大分子的形状和分子量。最后展望了这类大分子在生态学、工业与医学方面可能的应用。     

Oxygen Microscopy by Two‐Photon‐Excited Phosphorescence

High‐resolution images of oxygen distributions in microheterogeneous samples are obtained by two‐photon laser scanning microscopy (2P LSM), using a newly developed dendritic nanoprobe with internally enhanced two‐photon absorption (2PA) cross‐section. In this probe, energy is harvested by a 2PA antenna, which passes excitation onto a phosphorescent metalloporphyrin via intramolecular energy transfer. The 2P LSM allows sectioning of oxygen gradients with near diffraction‐limited resolution, and lifetime‐based acquisition eliminates dependence on the local probe concentration. The technique is validated on objects with a priori known oxygen distributions and applied to imaging of pO₂ in cells.     

Gene Delivery into T-Cells Using Ternary Complexes of DNA,Lipofectamine, and Carboxy-Terminal Phenylalanine-Modified Dendrimers

T-cells play critical roles in various immune reactions, and genetically engineered T-cells have attracted attention for the treatment of cancer and autoimmune diseases. Previously, it is shown that a polyamidoamine dendrimer of generation 4 (G4), modified with 1,2-cyclohexanedicarboxylic anhydride (CHex) and phenylalanine (Phe) (G4-CHex-Phe), is useful for delivery into T-cells and their subsets. In this study, an efficient non-viral gene delivery system is constructed using this dendrimer. Ternary complexes are prepared using different ratios of plasmid DNA, Lipofectamine, and G4-CHex-Phe. A carboxy-terminal dendrimer lacking Phe (G3.5) is used for comparison. These complexes are characterized using agarose gel electrophoresis, dynamic light scattering, and ζpotential measurements. In Jurkat cells, the ternary complex with G4-CHex-Phe at a P/COOH ratio of 1/5 shows higher transfection activity than other complexes, such as binary and ternary complexes with G3.5, without any significant cytotoxicity. The transfection efficiency of the G4-CHex-Phe ternary complexes decreases considerably in the presence of free G4-CHex-Phe and upon altering the complex preparation method. These results suggest that G4-CHex-Phe promotes the cellular internalization of the complexes, which is useful for gene delivery into T-cells.     

Nanogold-penetrated poly(amidoamine) dendrimer for enzyme-free electrochemical immunoassay of cardiac biomarker using cathodic stripping voltammetric method

Methods based on immunoassays have been developed for cardiac biomarkers, but most involve the low sensitivity and are unsuitable for early disease diagnosis. Herein we design an electrochemical immunoassay for sensitive detection of myoglobin (a cardiac biomarker for acute myocardial infarction) by using nanogold-penetrated poly(amidoamine) dendrimer (AuNP-PAMAM) for signal amplification without the need of natural enzymes. The assay was carried out on the monoclonal mouse anti-myoglobin (capture) antibody-anchored glassy carbon electrode using polyclonal rabbit anti-myoglobin (detection) antibody-labeled AuNP-PAMAM as the signal tag. In the presence of target myoglobin, the sandwiched immunocomplex could be formed between capture antibody and detection antibody. Accompanying AuNP-PAMAM, the carried gold nanoparticles could be directly determined via stripping voltammetric method under acidic conditions. Under optimal conditions, the detectable electrochemical signal increased with the increasing target myoglobin in the sample within a dynamic working range from 0.01 to 500 ng mL⁻¹ with a detection limit of 3.8 pg mL⁻¹. The electrochemical immunoassay also exhibited high specificity and good precision toward target myoglobin. Importantly, our strategy could be applied for quantitative monitoring of myoglobin in human serum specimens, giving well matched results with those obtained from commercialized enzyme-linked immunosorbent assay (ELISA) method.     

Self-organisation and alignment properties of homeotropically confined model liquid crystalline dendrimer systems

Controlling microscopic or macroscopic alignment of liquid crystalline dendrimers (LCDrs) in a porous media is an important feature for their possible potential applications. Here, we investigate structural and alignment behaviours of model LCDr system confined in a slit pore made of two parallel impenetrable walls. Isobaric–isothermal (NPT) Monte Carlo computational simulation method is used. A coarse-grained force field for inter-/intra-dendritic and LCDr-substrate interactions has been established. The inner surfaces of confining walls are made to induce homeotropic anchoring condition. According to simulation results, a variety of stable-ordered LCDr system states have been observed and analysed depending on the temperature and pressure.     

A Supramolecular Approach toward Bioinspired PAMAM‐Dendronized Fusion Toxins

Nature has provided a highly optimized toolbox in bacterial endotoxins with precise functions dictated by their clear structural division. Inspired by this streamlined design, a supramolecular approach capitalizing on the strong biomolecular (streptavidin (SA))–biotin interactions is reported herein to prepare two multipartite fusion constructs, which involves the generation 2.0 (D2) or generation 3.0 (D3) polyamidoamine‐dendronized transporter proteins (dendronized streptavidin (D3SA) and dendronized human serum albumin (D2HSA)) non‐covalently fused to the C3bot1 enzyme from Clostridium botulinum, a potent and specific Rho‐inhibitor. The fusion constructs, D3SA‐C3 and D2HSA‐C3, represent the first examples of dendronized protein transporters that are fused to the C3 enzyme, and it is successfully demonstrated that the C3 Rho‐inhibitor is delivered into the cytosol of mammalian cells as determined from the characteristic C3‐mediated changes in cell morphology and confocal microscopy. The design circumvents the low uptake of the C3 enzyme by eukaryotic cells and holds great promise for reprogramming the properties of toxin enzymes using a supramolecular approach to broaden their therapeutic applications.

     

Pharmacological Evaluation of Novel Organoiron Dendrimers as Antimicrobial and Anti‐Inflammatory Agents

The synthesis of a novel and attractive class of nonsteroidal anti‐inflammatory and antimicrobial organoiron dendrimers attached to the well‐known drug ibuprofen is achieved. The structures of these dendrimers are established by spectroscopic and analytical techniques. The antimicrobial activity of these dendrimers is investigated and tested against five human pathogenic Gram‐positive and Gram‐negative bacteria, and minimum inhibitory concentrations are reported. Some of these synthesized dendrimers exhibit higher inhibitory activity against methicillin‐resistant Staphylococcus aureus, vancomycin‐resistant Enterococcus faecium, and Staphylococcus warneri compare to the reference drugs. As well, the in vitro and in vivo anti‐inflammatory activities of these dendrimers are evaluated. The results of in vivo anti‐inflammatory activity and histopathology of inflamed paws show that all dendrimers display considerable anti‐inflammatory activity; however, second‐generation dendrimer ( G2‐D6 ) shows the best anti‐inflammatory activity, which is more potent than the commercial drug ibuprofen at the same tested dose. Results of the toxicity study reveal that G2‐D6  is the safest drug on biological tissues.     

Mimicking the Energy Funnel of the Photosynthetic Unit Using a Dendrimer-Dye Supramolecular Assembly

Photosynthesis involves light-harvesting complexes where an array of antenna pigment channels the absorbed solar energy to the reaction centre of a photosystem. This work reports a supramolecular dendrimer-dye assembly that mimics the natural light-harvesting mechanism. A dendrimeric molecule based on two-fluorophores has been constructed with three coumarin units at the end of three long arms and a 7-diethylaminocoumarin unit at the interior. The molecule self-aggregates in water into spherical micelles, which can encapsulate a rose-bengal dye (RB). On excitation, peripheral coumarin units shuttled the energy to the loaded RB dye reaction center via a two-step cascade resonance energy transfer (RET). The energy absorbed in the periphery is funnelled efficiently, resulting in a strong emission from the dye that resembles an energy funnel. The energy transfer cascade has been studied with both steady-state and time-resolved fluorescence spectroscopy. Molecular dynamics simulations of the self-assembled aggregates in water were also in agreement with the experimental observations.