Spectroscopic investigations of poly(propyleneimine)dendrimers using the solvatochromic probe phenol blue and comparisons to poly(amidoamine) dendrimers.

The physical and chemical properties of PPI dendrimers' interior were investigated using the fluorescent, solvatochromic probe phenol blue. In aqueous solutions of each generation studied, two discrete dye populations were clearly observed. PPI dendrimers were shown to form a tight, nonpolar association with the vast majority of available dye, within the dendrimer interior, near the core. In the steady-state fluorescence emission spectra, a microenvironment of decreasing polarity in increasingly larger-generation PPI dendrimers (up to G3) was seen for the associated probe. Each of the remaining larger-generation dendrimers provided a microenvironment of essentially equal polarity. Fluorescence anisotropy values for phenol blue in the PPI dendrimers demonstrated the dye's sensitivity to the changing molecular volumes of the dendrimer generations. Model compounds that mimicked PPI's surface groups and branching moieties were used to better define the associated dye's location. The mimics further confirmed that phenol blue was associated inside the dendrimer, where it did not interact with the dendrimer surface groups. The comparison of amine-terminated PPI and PAMAM dendrimers clearly demonstrated the effects of their structural differences and the ability of phenol blue to have sensed those differences, including the initiator core length, branching unit length, and branching unit chemical composition.     

Label-free and substrate-free potentiometric aptasensing using polycation-sensitive membrane electrodes

A potentiometric label-free and substrate-free (LFSF) aptasensing strategy which eliminates the labeling, separation, and immobilization steps is described in this paper. An aptamer binds specifically to a target molecule via reaction incubation, which could induce a change in the aptamer conformation from a random coil-like configuration to a rigid folded structure. Such a target binding-induced aptamer conformational change effectively prevents the aptamer from electrostatically interacting with the protamine binding domain. This could either shift the response curve for the potentiometric titration of the aptamer with protamine as monitored by a conventional polycation-sensitive membrane electrode or change the current-dependent potential detected by a protamine-conditioned polycation-sensitive electrode with the pulsed current-driven ion fluxes of protamine across the polymeric membrane. Using adenosine triphosphate (ATP) as a model analyte, the proposed concept offers potentiometric detection of ATP down to the submicromolar concentration range and has been applied to the determination of ATP in HeLa cells. In contrast to the current LFSF aptasensors based on optical detection, the proposed strategy allows the LFSF biosensing of aptamer/target binding events in a homogeneous solution via electrochemical transduction. It is anticipated that the proposed strategy will lay a foundation for development of potentiometric sensors for LFSF aptasensing of a variety of analytes where target binding-induced conformational changes such as the formation of folded structures and the opening of DNA hairpin loops are involved.     

Encapsulation of curcumin within poly(amidoamine) dendrimers for delivery to cancer cells

Curcumin has anti-proliferative and pro-apototic properties against a variety of cancer cells in vitro. Unfortunately, the water-insolubility and instability leads to its low bioavailability in vivo tests. Here, we report a general approach to using poly(amidoamine) dendrimer with acetyl terminal groups to encapsulate curcumin(G₅-Ac/Cur) for drug delivery to cancer cells. The solubility, release kinetics, anticancer activity, and apoptotic-related protein expression (Bax and Bcl-2) were investigated in detail. Comparing with curcumin, the water-solubility value of G₅-Ac/Cur increased 200-fold, and the release of curcumin from the complexes was in a sustained manner. G₅-Ac/Cur showed higher anti-proliferative activity against A549 cell lines and had the better effect on the generation of intracellular reactive oxygen species, the mitochondrial membrane potential and cell apoptosis. Furthermore, the ratio of Bax/Bcl-2 was higher in samples treated with G₅-Ac/Cur. The results indicated that the G₅-Ac drug delivery system could improve the solubility and anti-cancer effect of curcumin.     

温敏型聚酰胺-胺型树状聚合物的研究进展

温敏聚酰胺-胺型(PAMAM)树状聚合物是同时具有温敏特性和树状大分子性能的一类聚合物,其不但受温度变化会发生刺激响应,同时具有PAMAM树状聚合物多反应位点、低粘度、高支化度、特殊的三维结构等特点。这类聚合物在医用材料、纺织面料、温敏传感器等领域有着广泛的应用前景。温敏聚PAMAM树状聚合物的制备方法丰富多样,可以采用调节树状聚合物末端基元取代度、或者调节聚合物中亲水链段的比例、或在树状大分子末端接枝具有温敏性的物质等方法。本文就温敏型PAMAM树状聚合物的制备方法、温敏机理及应用领域等方面进行综述。     

Growth of multi-amine terminated poly(amidoamine) dendrimers on the surface of carbon nanotubes

An in situ repetitive divergent polymerization strategy was employed to grow multi-amine poly(amidoamine) dendritic macromolecules on the surfaces of multiwalled carbon nanotubes (MWNTs), affording novel three-dimensional (3D) molecular nanocomposites. The crude MWNTs were oxidized using H(2)SO(4)/HNO(3) = 3:1?(v/v) and then reacted with thionyl chloride, resulting in MWNTs functionalized with chlorocarbonyl groups (MWNT-COCl). MWNT-COCl, when reacted with an excess of ethylenediamine, produced amine-functionalized MWNT supported initiators (MWNT-NH(2)). Using the MWNT-NH(2) as the growth supporter and methylacrylate/ethylenediamine as building blocks, multi-amine dendritic poly(amidoamine) macromolecules were covalently grafted onto the sidewalls and ends of MWNTs via Michael addition reaction and amidation. Thermal gravimetric analysis (TGA) measurements showed that the weight ratio of the as-grown dendritic polymers on the MWNT surfaces lay in the 10%-50% range. The products were also characterized by Fourier transform infrared (FTIR), Raman, nuclear magnetic resonance (NMR), and transmission electron microscopy (TEM) analysis. The results indicate that the dendrimers are grafted onto the surface of MWNTs. The as-prepared nanocomposites exhibit excellent dispersibility in water.     

Stability, antimicrobial activity, and cytotoxicity of poly(amidoamine) dendrimers on titanium substrates

In this article, we present the first report on the antibacterial activity and cytotoxicity of poly(amidoamine) (PAMAM) dendrimers immobilized on three types of titanium-based substrates with and without calcium phosphate coating. We show that the amino-terminated PAMAM dendrimers modified with various percentages (0-60%) of poly(ethylene glycol) (PEG) strongly adsorbed on the titanium-based substrates. The resultant dendrimer films effectively inhibited the colonization of the Gram-negative bacteria Pseudomonas aeruginosa (strain PAO1) and, to a lesser extent, the Gram-positive bacteria Staphylococcus aureus (SA). The antibacterial activity of the films was maintained even after storage of the samples in PBS for up to 30 days. In addition, the dendrimer films had a low cytotoxicity to human bone mesenchymal stem cells (hMSCs) and did not alter the osteoblast gene expression promoted by the calcium phosphate coating.     

HPLC separation of different generations of poly(amidoamine) dendrimers modified with various terminal groups

Polyamidoamine (PAMAM) dendrimers of different generations with various terminal groups were analyzed, for the first time, using a combination of high-performance liquid chromatography (HPLC), size exclusion chromatography (SEC), and matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) techniques. Separation of amine-terminated dendrimers from generation 1 through generation 9 (G1NH(2)-G9NH(2)) was achieved using reversed-phase HPLC with elution time increasing gradually as the density of terminal amine groups increases as a function of generation. Furthermore, separation of dendrimers with terminal amino, acetamide, hydroxyl, and carboxylate groups was obtained. It has also been shown that HPLC can be used to separate dendrimers based on some structural defects inherent during the syntheses of PAMAM dendrimers. MALDI-TOF mass spectra of G1NH(2) identify the major imperfections present during typical synthesis processes. The absolute molar masses (M(n)) and molar mass distributions of the dendrimers were measured using the SEC system equipped with multiangle laser light scattering and refractive-index detectors. Findings from this study suggest HPLC can be a vital tool for characterization and preparative separation of PAMAM dendrimers.     

De novo growth of poly(amidoamine) dendrimers on the surface of multi-walled carbon nanotubes

Carbon nanotubes (CNTs) are often used after modification. Poly(amidoamine) (PAMAM) dendrimers modified CNTs have attracted attentions due to their rich terminal amino groups. However, direct grafting of PAMAM dendrimers on CNTs’ surface is limited by the steric hindrance and its supply. De novo growth of PAMAM on multi-walled carbon nanotubes (MWCNTs), i.e., PAMAM@CNTs, is expected to eliminate the limits since the adopted reagents are readily available small molecular chemicals. It was realized using a divergent method and a “grafting from” technique by alternate amidization of terminal ester groups with ethylenediamine and Michael addition of methyl acrylate to the yielding amino groups. Spectral analysis, including Fourier transform infrared, Raman, hydrogen nuclear magnetic resonance, and X-ray photo-electron spectroscopy, verified that the functional groups were covalently grafted on the surface of MWCNTs, while thermogravimetric and elemental analysis showed that these groups were exponentially grown on MWCNTs, suggesting the formation of a dendritic PAMAM. Besides, high resolution transmission electron microscopy also confirmed that the spherical PAMAM was formed on the CNTs’ surface and an average particle size of 15–20 nm for G8.0-dendrimers was obtained.     

Spectroscopic characterization of poly(amidoamine) dendrimers as selective uptake devices: Phenol blue versus Nile red

Selectivity of amine-terminated poly(amidoamine) (PAMAM-AT) dendrimers as host molecules for phenol blue and Nile red guests was investigated using absorption and fluorescence spectroscopies. Phenol blue has been known to associate near the core in the PAMAM-AT dendrimers. Nile red has also been shown to associate with this dendrimer family; however, this occurs in the outermost branches. Concentration ratios and generational dependencies were investigated. It was found that phenol blue was sequestered in the PAMAM-AT dendrimers in the presence of the interfering Nile red, and this association appeared to be the same as that of PAMAM-AT with phenol blue alone. As the concentration of Nile red increased relative to the concentration of phenol blue, the desired association of phenol blue became increasingly hindered. While the presence of Nile red did affect association, phenol blue still had considerable association even when Nile red was in ten-fold excess. The association of phenol blue with PAMAM-AT was stable and robust; however, Nile red's association was relatively weak and unstable.     

树状聚合物PAMAM制备高脱盐纳滤膜

通过发散法合成了以N-(2-胺乙基)哌嗪为核的端胺基树状聚合物聚酰胺胺(PAMAM),并以此为水相单体与均苯三甲酰氯发生界面聚合反应制备了高脱盐率纳滤膜.采用傅里叶转换红外光谱(FTIR-ATR)、X射线光电子能谱(XPS)等手段研究膜表面化学组成的变化,扫描电镜(SEM),原子力显微镜(AFM)观察膜的结构与形貌,接触角测定仪评价膜的亲水性.结果表明,使用高代数PAMAM、增大PAM-AM浓度、延长反应时间均促使膜的致密度增加,脱盐卒增大.使用浓度为4.46×10-3mol/L第二代PAM-AM溶液为反应物制备的纳滤膜对Na2SO4、MgCl2、MgSO4的脱除率分别达到93.0%,92.3%和91.4%.值得注意的是,PAMAM浓度的增加导致酰氯基由过量到相对不足,最终所制备的纳滤膜对NaCl、Na2SO4、MgCl2和MgSO4等4种盐的脱盐顺序也发生相应变化,主要体现在MgCl2的脱除率由低于Na2SO4和MgSO4变化到高于这两种盐最后三者的脱除率趋于近似相等,均>90%.     

Optimization of carboxylate-terminated poly(amidoamine) dendrimer-mediated cisplatin formulation

Cisplatin is mainly used in the treatment of ovarian, head and neck and testicular cancer. Poor solubility and non-specific interactions causes hurdles in the development of successful cisplatin formulation. There were few reports on poly(amidoamine) (PAMAM) dendrimer–cisplatin complexes for anticancer treatment. But the earlier research was mainly focused on therapeutic effect of PAMAM dendrimer–cisplatin complex, with less attention paid on the formulation development of these complexes. Objective of the present study is to optimize and validate the carboxylate-terminated, EDA core PAMAM dendrimer-based cisplatin formulation with respect to various variables such as dendrimer core, generation, drug entrapment, purification, yield, reproducibility, stability, storage and in-vitro release. Dendrimer–cisplatin complex was prepared by an efficient method which significantly increases the % platinum (Pt) content along with the product yield. Dendrimers showed reproducible (～27%) platinum loading by weight. Variation in core and generations does not produce significant change in the % Pt content. Percentage Pt content of dendrimeric formulation increases with increase in drug/dendrimer mole ratio. Formulation with low drug/dendrimer mole ratio showed delayed release compared to the higher drug/dendrimer mole ratio; these dendrimer formulations are stable in room temperature. In vitro release profiles of the stored dendrimer–cisplatin samples showed comparatively slow release of cisplatin, which may be due to formation of strong bond between cisplatin and dendrimer. This study will contribute to create a fine print for the formulation development of PAMAM dendrimer–cisplatin complexes.     

Effect of sodium dodecylsulfate and dodecyltrimethyl ammonium bromide on the morphologies of gold nanoparticles in the presence of poly(amidoamine) dendrimers

The synthesis of gold nanoparticles has been carried out in aqueous phase in the presence of both ionic surfactants (i.e., sodium dodecylsulfate (SDS) and dodecyltrimethylammonium bromide (DTAB)) and poly(amidoamine) dendrimers (PAMAM). It has been observed that the fluoroderivative of 2G PAMAM (2D) acts as reducing agent in reducing Au(lll) to Au(0) leading to the formation of fine gold nanoparticles. This process has been further evaluated in the presence of fixed amounts of both SDS and DTAB in their respective pre and post micellar concentration regions. The presence of SDS leads to the appearance of clear ordered morphologies such as triangular, hexagonal, spherical, and rod shaped, while the presence of DTAB does not show this effect. The formation of nanoparticles in triangular morphologies is more significant in the premicellar concentration range of SDS whereas hexagonal morphologies in the post micellar concentration range. On the contrary, increase in the DTAB concentration from pre to post micellar range only reduces the size of gold nanoparticles without the appearance of any ordered morphology. The formation of ordered gold nanoparticles in the presence of SDS has been further attributed to the significant SDS-dendrimer interactions and an appropriate mechanism has been proposed to justify the results.     

聚酰胺-胺型树枝状分子的合成及其水溶液表面张力的研究

实验合成了以乙二胺(EDA)为核的1.0～3.0代聚酰胺-胺型树枝状分子,对合成的产品进行了核磁、红外、元素分析等表征.采用Wilhelmy吊板法测定了整代1.0～3.0代不同浓度下聚酰胺-胺型树枝状分子水溶液的表面张力,探讨了不同代数聚酰胺-胺型树枝状分子的表面活性.实验表明整代聚酰胺-胺型树枝状分子表面活性很小,但是2.0代分子水溶液的表面张力比同浓度的1.0代和3.0代分子水溶液的表面张力都低,而不是按由低代到高代的顺序递减.     

Potentiometric response of conducting polymer electrodes for oxygen in neutral aqueous solutions

The effect of oxygen on the potential of electrodes coated with a thin layer of various conducting polymers and immersed in aqueous neutral buffer solution has been studied. A theoretical equation describing the dependence of the potential on the concentration of oxygen has been derived and shown to be in conformity with the experimental results for polyaniline, polypyrrole, and poly(3-methylthiophene). The theory is based on the formation of charge-transfer complexes between oxygen molecule and the reduced (undoped) form of conducting polymer.     

Potentiometric titrations in a poly(dimethylsiloxane)-based microfluidic device

This paper describes a microfluidic device, fabricated in poly(dimethylsiloxane), that is used for potentiometric titrations. This system generates step gradients of redox potentials in a series of microchannels. These potentials are probed by microelectrodes that are integrated into the chip; the measured potentials were used to produce a titration curve from which the end point of a reaction was measured.     

Kinetic and equilibrium binding analysis of protein-ligand interactions at poly(amidoamine) dendrimer monolayers

The interaction of streptavidin (SA) with a biotinylated surface has been of great interest in the development of an interfacial layer for protein immobilization based on self-assembled monolayers (SAMs) and polymeric layers. Here, we demonstrate the unique characteristics of protein-ligand interactions on dendrimer monolayers based on kinetic and equilibrium binding analyses. With amine-ended poly(amidoamine) dendrimers from the first (G1) to fourth (G4) generation, the formation of even, compact dendrimer monolayers on gold was confirmed using FT-IR spectroscopy and ellipsometry. For the SA-biotin interaction, quantitative analysis of bound SA using surface plasmon resonance showed that the saturation binding level of SA was fairly higher in all dendrimer layers when compared to other tested systems of 11-mercaptoundecylamine SAMs and a poly(L-lysine) layer. Kinetic studies revealed that the initial binding rate of SA up to the saturation level was 2-fold higher in all dendrimer layers than in the SAMs regardless of the surface density of functionalized biotin. Concurrently, the dendrimer layers led to much higher values of sticking probability, which is defined as the probability that the SA molecule adsorbs upon collision with a biotinylated surface, at a fixed SA coverage, and prolonged the significant levels around the maximum probability with increasing SA coverage. Plots of the saturation coverage of SA versus the SA concentration in solution showed that SA binding onto the biotinylated G1 and G3 layers fit to a Langmuir isotherm model. Taken together, faster binding of SA and highly ordered packing of the molecules seems to be achieved through typical properties of the dendrimer monolayers such as surface distribution of functionalized biotin, surface corrugation, and flexibility of highly branched larger dendrimers, which provides a guideline for the construction and analysis of an interfacial layer in biosensing applications.     

Poly(amidoamine)-G5 dendrimers/noble metal gold hybrid nanoparticles prepared by γ-ray irradiation

In the absence of a chemical reductant and other protective reagents, noble metal gold hybrid nanoparticles are successfully prepared by ⁶⁰Co γ-ray irradiation using fifth-generation poly(amidoamine) dendrimer with surface amine-terminated group as polymeric template. The zerovalent gold is of spherical structure and the particle size is on nanometer scale range of 3-12 nm. The size distribution of gold nanoparticles displays multidispersity. The results of FTIR show that interactions between dendrimer template and gold nanoparticle exist in intra-molecule and inter-molecule of fifth-generation poly(amidoamine) dendrimer.     

树枝状大分子改性聚乙二醇生物材料的制备与研究

采用了新的"酸酐法"使用2,2-二羟甲基丙酸(DMPA)来合成一种具有规整结构树枝状大分子.制备好的树枝状大分子通过高效酯化反应接枝到聚乙二醇(PEG)两端,形成结构高度支化、表面官能团密度大、单分散性的大分子.树枝状大分子的制备过程中的分步提纯进行彻底,反应物在高效催化剂(DMAP)的存在下反应活性大,反应完全,得到的产物极其规整.之后用一步合成方法得到了树枝状大分子-聚乙二醇-树枝状大分子(dendrimers-PEG-dendrimers)的聚合物.通过红外光谱(FTIR)、核磁共振氢谱(1H-NMR)、凝胶渗透色谱(GPC)对聚合物及其中间产物的表征表明,合成的高分子结构严密地与理论相吻合.