A study of antimicrobial property of textile fabric treated with modified dendrimers

Dendrimers have been used as a vehicle to develop the antimicrobial properties of textile fabrics. We have taken advantage of the large number of functional groups present in the regular and highly branched three‐dimensional architecture of dendrimers. In this study, the poly(amidoamine) (PAMAM) G‐3 dendrimer was modified to provide antimicrobial properties. Following a procedure similar to what is suggested in the literature, PAMAM (G3) with primary amine end groups was converted into ammonium functionalities. The modification was then confirmed by FTIR and ¹³C‐NMR analysis. Dendrimers have unique properties owing to their globular shape and tunable cavities, this allows them to form complexes with a variety of ions and compounds; and also act as a template to fabricate metal nanoparticles. AgNO₃–PAMAM (G3) complex as well as a MesoSilver–PAMAM (G3) complex were formed and these modified dendrimers were characterized by a UV–Visible spectrophotometer to study the complex formation. Modified dendrimers were applied to the Cotton/Nylon blend fabric. SEM and EDX analysis were performed to study the dispersion of silver nanoparticles onto the fabric. An antimicrobial test of the treated‐fabric against Staphylococcus aureus exhibited significant biocidal activities for each type of modified‐dendrimer. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Gadolinium‐conjugated FA‐PEG‐PAMAM‐COOH nanoparticles as potential tumor‐targeted circulation‐prolonged macromolecular MRI contrast agents

The aim of research is to develop potential tumor‐targeted circulation‐prolonged macromolecular magnetic resonance imaging (MRI) contrast agents without the use of low molecular gadolinium (Gd) ligands. The contrast agents were based on polymer–metal complex nanoparticles with controllable particle size to achieve the active and passive tumor‐targeted potential. In particular, poly (amidoamine) (PAMAM) dendrimer with 32 carboxylic groups was modified with folate‐conjugated poly (ethyleneglycol) amine (FA‐PEG‐NH₂, M_w: 2 k and 4 kDa). FA‐PEG‐PAMAM‐Gd macromolecular MRI contrast agents were prepared by the complex reaction between the carboxylic groups in PAMAM and GdCl₃. The structure of FA‐PEG‐PAMAM‐COOH was confirmed by nuclear magnetic resonance (¹H‐NMR), Fourier transform infrared (FTIR) spectra, and electrospray ionization mass spectra (ESI‐MS). The mass percentage content of Gd (III) in FA‐PEG‐PAMAM‐Gd was measured by inductively coupled plasma‐atomic emission spectrometer (ICP‐AES). The sizes of these nanoparticles were about 70 nm measured by transmission electron microscopy, suggestion of their passive targeting potential to tumor tissue. In comparison with clinically available small molecular Gadopentetate dimeglumine, FA‐PEG‐PAMAM‐Gd showed comparable cytotoxicity and higher relaxation rate, suggestion of their great potential as tumor‐targeted nanosized macromolecular MRI contrast agents due to the overexpressed FA receptor in human tumor cell surfaces. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Efficient Transfection of siRNA by Peptide Dendrimer–Lipid Conjugates

Efficient delivery of small interfering RNA (siRNA) into cells is the basis of target‐gene‐specific silencing and, ultimately, gene therapy. However, current transfection reagents are relatively inefficient, and very few studies provide the sort of systematic understanding based on structure–activity relationships that would provide rationales for their improvement. This work established peptide dendrimers (administered with cationic lipids) as siRNA transfection reagents and recorded structure–activity relationships that highlighted the importance of positive charge distribution in the two outer layers and a hydrophobic core as key features for efficient performance. These dendrimer‐based transfection reagents work as well as highly optimised commercial reagents, yet show less toxicity and fewer off‐target effects. Additionally, the degrees of freedom in the synthetic procedure will allow the placing of decisive recognition features to enhance and fine‐tune transfection and cell specificity in the future.     

Polymeric siRNA delivery vectors: knocking down cancers with polymeric‐based gene delivery systems

One of the most promising routes for cancer therapy that has evolved over the previous decade is the use of small‐interfering RNA (siRNA) as a means of switching off genes that are responsible for tumour development. However, while siRNA and gene/antisense therapies provide alternatives to conventional chemotherapies, significant hurdles related to the delivery and efficacy of treatment must still be overcome before this technology can be used as an effective treatment for cancer and other diseases. This review highlights the issues associated with siRNA therapy in vivo, and describes the various approaches that are being explored using polymers as delivery vectors. In particular, the review focuses on targeted delivery as a means of improving efficacy of the gene therapy. © 2014 Society of Chemical Industry     

Enhanced Electrocatalysis for Methanol Oxidation on Ordered {[PdPW11O39]5–/Pt/PAMAM}n Multilayer Composites

The {[PdPW₁₁O₃₉]^5–/Pt/PAMAM}_n multilayer composites constructed from G4.0 Amino‐terminated poly (amidoamine) dendrimer (PAMAM), Pt and Keggin‐type palladium(II)‐substituted polyoxometalates anion ([PdPW₁₁O₃₉]^5–) were prepared via layer by layer electro‐depositing technique. The X‐ray photoelectron spectroscopy (XPS), X‐ray diffraction (XRD), and field emission scanning electron microscope (FE‐SEM) characterization indicate that the Pt nanoparticles have been anchored on the as‐prepared nanocomposites. And the morphologies of Pt nanoparticles are influenced by deposition potential, the number of layers of {[PdPW₁₁O₃₉]^5–/Pt/PAMAM}_n multilayer nanocomposites, and the existence of PAMAM. The electrocatalytic properties and stability of {[PdPW₁₁O₃₉]^5–/Pt/PAMAM}_n multilayer nanocomposites were investigated by cyclic voltammetry. Experimental investigation results reveal that PAMAM is a good support for Pt nanoparticle growth due to its interior cavity structure and high stability. [PdPW₁₁O₃₉]^5– play an important role to prevent intermediate product (mainly as CO) in the methanol oxidation from poisoning the as‐prepared catalyst. The {[PdPW₁₁O₃₉]^5–/Pt/PAMAM}₃/GC shows better electrocatalytic properties, stability, and CO tolerance ability than Pt/GC and {Pt/PAMAM}₃/GC fabricated by similar electrodeposition processes.     

Gene Therapy in HIV‐Infected Cells to Decrease Viral Impact by Using an Alternative Delivery Method

The ability of dendrimer 2G‐[Si{O(CH₂)₂N(Me)₂⁺(CH₂)₂NMe₃⁺(I^?)₂}]₈ (NN16) to transfect a wide range of cell types, as well as the possible biomedical application in direct or indirect inhibition of HIV replication, was investigated. Cells implicated in HIV infection such as primary peripheral blood mononuclear cells (PBMC) and immortalized suspension cells (lymphocytes), primary macrophages and dendritic cells, and immortalized adherent cells (astrocytes and trophoblasts) were analyzed. Dendrimer toxicity was evaluated by mitochondrial activity, cell membrane rupture, release of lactate dehydrogenase, erythrocyte hemolysis, and the effect on global gene expression profiles using whole‐genome human microarrays. Cellular uptake of genetic material was determined using flow cytometry and confocal microscopy. Transfection efficiency and gene knockdown was investigated using dendrimer‐delivered antisense oligonucleotides and small interfering RNA (siRNA). Very little cytotoxicity was detected in a variety of cells relevant to HIV infection and erythrocytes after NN16 dendrimer treatment. Imaging of cellular uptake showed high transfection efficiency of genetic material in all cells tested. Interestingly, NN16 further enhanced the reduction of HIV protein 24 antigen release by antisense oligonucleotides due to improved transfection efficiency. Finally, the dendrimer complexed with siRNA exhibited therapeutic potential by specifically inhibiting cyclooxygenase‐2 gene expression in HIV‐infected nervous system cells. NN16 dendrimers demonstrated the ability to transfect genetic material into a vast array of cells relevant to HIV pathology, combining high efficacy with low toxicity. These results suggest that NN16 dendrimers have the potential to be used as a versatile non‐viral vector for gene therapy against HIV infection.     

Effect of dendrimer‐like PAMAM grafted attapulgite on the microstructure and morphology of Nylon‐6

The effect of dendrimer‐like polyamidoamine grafted attapulgite (ATP‐PAMAM) on the microstructure and morphology of Nylon‐6 (PA6) was investigated. The ATP‐PAMAM nanoparticles were prepared by treating attapulgite (ATP) with heat and acid followed by grafting with polyamidoamine (PAMAM) molecules, which was confirmed by Fourier transform infrared spectroscopy (FT‐IR), thermogravimetric analysis (TGA), and dispersion state in formic acid. The X‐ray diffraction (XRD) analysis result indicated that the grafting modification was occurred on the surface of fibrous crystals and did not shift the crystal structure of ATP. PA6/ATP‐PAMAM (G_2.0) nanocomposites with different modified ATP content were prepared by melt compounding in a twin screw extruder. XRD measurements suggested that the intensity of diffraction peak of α crystalline form of PA6 decreased gradually as the inclusion of ATP‐PAMAM(G_2.0) into the PA6 matrix, while that of γ crystalline form increased gradually. The results of molau experiment and scanning electron microscopy (SEM) observation showed not only a uniform dispersion of ATP‐PAMAM(G_2.0) in the PA6 matrix but also a strong interfacial adhesion between them. Mechanical investigation (by tensile test) showed an obvious improvement in the presence of surface modified ATP. POLYM. COMPOS., 35:627–635, 2014. © 2013 Society of Plastics Engineers     

Functional dendrimer–gold nanoparticle hybrids for biomedical applications

Dendrimers are a class of nano‐sized synthetic polymers with a well‐defined composition and regularly branched tree‐like structure produced by stepwise growth. The uniform size, globular shape and tunable surface chemistry make dendrimers versatile nanoscaffolds to encapsulate or stabilize various inorganic (metal, metal oxide, semiconductor) nanoparticles. In the past decade, research interest in dendrimer–inorganic nanoparticle hybrids has evolved from the development of interesting properties to the exploitation of advanced and useful functions. In particular, because gold nanoparticles with controlled morphology and optical properties have been demonstrated to be promising and versatile candidates for a diverse field of biomedical applications including sensing, in vitro and in vivo imaging, drug delivery, diagnostics and therapies, dendrimer–gold nanoparticle hybrids with biocompatibility have recently been intensively investigated for promising biomedical applications due to their controllable structures and dimensions, as well as their desirable internal and/or external functionalities. In this review, we discuss the recent progress regarding the development of functional dendrimer–gold nanoparticle hybrids for biomedical applications. The strategies for the fabrication of various structures of dendrimer–gold nanoparticle hybrids will first be summarized, followed by their biomedical applications in drug and gene delivery, photothermal therapy and combined therapies. © 2018 Society of Chemical Industry     

Antitumor efficacy of doxorubicin encapsulated within PEGylated poly(amidoamine) dendrimers

We report here a general approach to using poly(amidoamine) (PAMAM) dendrimers modified with polyethylene glycol (PEG) as a platform to encapsulate an anticancer drug doxorubicin (DOX) for in vitro cancer therapy applications. In this approach, PEGylated PAMAM dendrimers were synthesized by conjugating monomethoxypolyethylene glycol with carboxylic acid end group (mPEG‐COOH) onto the surface of generation 5 amine‐terminated PAMAM dendrimer (G5.NH₂), followed by acetylation of the remaining dendrimer terminal amines. By varying the molar ratios of mPEG‐COOH/G5.NH₂, G5.NHAc‐mPEG_n (n = 5, 10, 20, and 40, respectively) with different PEGylation degrees were obtained. We show that the PEGylated dendrimers are able to encapsulate DOX with approximately similar loading capacity regardless of the PEGylation degree. The formed dendrimer/DOX complexes are water soluble and stable. In vitro release studies show that DOX complexed with the PEGylated dendrimers can be released in a sustained manner. Further cell viability assay in conjunction with cell morphology observation demonstrates that the G5.NHAc‐mPEG_n/DOX complexes display effective antitumor activity, and the DOX molecules encapsulated within complexes can be internalized into the cell nucleus, similar to the free DOX drug. Findings from this study suggest that PEGylated dendrimers may be used as a general drug carrier to encapsulate various hydrophobic drugs for different therapeutic applications. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40358.     

Preparation of new dendrimer‐like star‐shaped amphiphilic poly(ethylene glycol)–poly(ϵ‐caprolactone) copolymers for biocompatible and high‐efficiency curcumin delivery

Novel amphiphilic star‐shaped terpolymers comprised of hydrophobic poly(?‐caprolactone), pH‐sensitive polyaminoester block and hydrophilic poly(ethylene glycol) (M_n = 1100, 2000 g mol^?1) were synthesized using symmetric pentaerythritol as the core initiator for ring‐opening polymerization (ROP) reaction of ?‐caprolactone functionalized with amino ester dendrimer structure at all chain ends. Subsequently, a second ROP reaction was performed by means of four‐arm star‐shaped poly(?‐caprolactone) macromer with eight ‐OH end groups as the macro‐initiator followed by the attachment of a poly(ethylene glycol) block at the end of each chain via a macromolecular coupling reaction. The molecular structures were verified using Fourier transform infrared and ¹H NMR spectroscopies and gel permeation chromatography. The terpolymers easily formed core–shell structural nanoparticles as micelles in aqueous solution which enhanced drug solubility. The hydrodynamic diameter of these agglomerates was found to be 91–104 nm, as measured using dynamic light scattering. The hydrophobic anticancer drug curcumin was loaded effectively into the polymeric micelles. The drug‐loaded nanoparticles were characterized for drug loading content, encapsulation efficiency, drug–polymer interaction and in vitro drug release profiles. Drug release studies showed an initial burst followed by a sustained release of the entrapped drug over a period of 7days at pH = 7.4 and 5.5. The release behaviours from the obtained drug‐loaded nanoparticles indicated that the rate of drug release could be effectively controlled by pH value. Altogether, these results demonstrate that the designed nanoparticles have great potential as hydrophobic drug delivery carriers for cancer therapy. © 2015 Society of Chemical Industry     

Binding properties of polyamidoamine dendrimers

Dendrimers are globular, hyperbranched polymers possessing a high concentration of surface functional groups and internal cavities. These unique features make them good host molecules for small ligands. To reveal relationships between dendrimer size and its encapsulating properties, the interactions of the fourth and the sixth generations of polyamidoamine dendrimers (PAMAM G4 and PAMAM G6) with a fluorescent dye 1‐anilinonaphthalene‐8‐sulfonate (ANS) were studied. Because ANS is a fluorescent molecule and its fluorescence is very sensitive to changes in its microenvironment, it was possible to use spectrofluorometric methods to evaluate the interactions with dendrimers. A double fluorometric titration method was used to estimate a binding constant and the number of binding centers. There were two types of dendrimer binding centers characterized by different affinity towards ANS. For PAMAM G4, the values of K_b and n for low‐affinity and high‐affinity sites equaled to 2.6 × 10⁵, 0.60 and 3.70 × 10⁶, 0.34, respectively, whereas in the case of PAMAM G6, these values equaled to 1.2 × 10⁵, 76.34 and 1.38 × 10⁶, 22.73. It was observed that the size of the dendrimer had a strong impact on the number of ANS molecules that interacted with dendrimers and their location within the macromolecule. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 2036–2040, 2007     

A structure/function study of polyaminoamide dendrimers as silica scale growth inhibitors

Dendrimers have attracted immense attention during the last decade due to their interesting properties both from a basic and an applied research viewpoint. Encapsulation of metal nanoparticles for catalysis, drug delivery and light harvesting are only some applications of dendrimers that are breaking new ground. A novel application of dendrimer technology is described in the present paper that relates to industrial water treatment. Industrial water systems often suffer from undesirable inorganic deposits. These can form either in the bulk or on metallic surfaces, such as heat exchangers or pipelines. Silica (SiO₂) scale formation and deposition is a major problem in high‐silica‐containing cooling waters. Scale prevention rather than removal is highly desired. In this paper, benchtop screening tests on various silica inhibition chemistries are reported, with emphasis on materials with a dendrimeric structure. Specifically, the inhibition properties of commercially available STARBURST^® polyaminoamide (PAMAM) dendrimers generations 0.5, 1, 1.5, 2, and 2.5 are investigated in detail together with other commonly‐used scale inhibitors. Experimental results show that inhibition efficiency largely depends on structural features of PAMAM dendrimers such as generation number and nature of the end groups. PAMAM dendrimers are effective inhibitors of silica scale growth at 40 ppm dosage levels. PAMAM dendrimers also act as silica nucleators, forming SiO₂–PAMAM composites. This occurs because the SiO₂ formed by incomplete inhibition interacts with cationic PAMAM‐1 and ‐2. The general scope of silica formation and inhibition in industrial waters is also discussed. Copyright © 2005 Society of Chemical Industry     

Synthesis and Antitumor Activity of Ether Glycerophospholipids Bearing a Carbamate Moiety at the sn‐2 Position: Selective Sensitivity Against Prostate Cancer Cell Lines

Analogues of 1‐O‐hexadecyl‐sn‐3‐glycerophosphonocholine (compounds 1 – 4 ) or sn‐3‐glycerophosphocholine (compound 5 ) bearing a carbamate or dicarbamate moiety at the sn‐2 position were synthesized and evaluated for their antiproliferative activity against cancer cells derived from a variety of tissues. Although all of the compounds are antiproliferative, surprisingly the carbamates ( 1 and 2 ) are more effective against the hormone‐independent cell lines DU145 and PC3 than toward other cancer cell lines we examined. This selectivity was not observed with the dicarbamates ( 3 and 4 ). Phosphocholine carbamate analogue 5 is as effective against the prostate cancer cell lines as the corresponding phosphonocholine analogue 1 . Cell death induced by 2′‐(trimethylammonio)ethyl 4‐hexadecyloxy‐3(R)‐N‐methylcarbamoyl‐1‐butanephosphonate (carbamate analogue 2 ) appeared to be mediated by apoptosis, as assessed by caspase activation and loss of mitochondrial membrane potential. The in vivo activity of 2 was evaluated in a murine prostate cancer xenograft model. Oral and intravenous administration showed that 2 is effective in inhibiting the growth of PC3 tumors in Rag2M mice. Our studies show that the glycerolipid carbamates reported herein represent a class of prostate‐cancer‐selective cytotoxic agents.     

Liver‐targeting doxorubicin‐conjugated polymeric prodrug with pH‐triggered drug release profile

The aim of the research presented was to develop a potential liver‐targeting prolonged‐circulation polymeric prodrug of doxorubicin (Dox) with a pH‐triggered drug release profile. In particular, linear dendritic block copolymers composed of polyamidoamine dendrimer (PAMAM) and poly(ethylene glycol) (PEG; number‐average molecular weight of 2000 g mol^?1) with or without galactose (Gal) were synthesized. Dox was coupled to the copolymers via an acid‐labile hydrazone linker. These prodrugs, designated Gal‐PEG‐b‐PAMAM‐Dox_n and mPEG‐b‐PAMAM‐Dox_m, showed accelerated Dox release as the pH decreased from 8.0 to 5.6. Cytotoxicity of the prodrugs was lower than that of free Dox due to the gradual drug release nature. Compared to mPEG‐b‐PAMAM‐Dox_m, Gal‐PEG‐b‐PAMAM‐Dox_n showed rather high cytotoxicity against Bel‐7402, suggestive of its galactose receptor‐mediated enhanced tumor uptake. This galactose receptor‐mediated liver‐targeted profile was further confirmed by the prolonged retention time in hepatoma tissue monitored using magnetic resonance imaging. Gal‐PEG‐b‐PAMAM‐Dox_n showed better in vivo antitumor efficacy than free Dox, suggesting its great potential as a polymeric antitumor prodrug. Copyright © 2010 Society of Chemical Industry     

Biodegradable Nanoparticles of mPEG-PLGA-PLL Triblock Copolymers as Novel Non-Viral Vectors for Improving siRNA Delivery and Gene Silencing

Degradation of mRNA by RNA interference is one of the most powerful and specific mechanisms for gene silencing. However, insufficient cellular uptake and poor stability have limited its usefulness. Here, we report efficient delivery of siRNA via the use of biodegradable nanoparticles (NPs) made from monomethoxypoly(ethylene glycol)-poly(lactic-co-glycolic acid)-poly-l-lysine (mPEG-PLGA-PLL) triblock copolymers. Various physicochemical properties of mPEG-PLGA-PLL NPs, including morphology, size, surface charge, siRNA encapsulation efficiency, and in vitro release profile of siRNA from NPs, were characterized by scanning electron microscope, particle size and zeta potential analyzer, and high performance liquid chromatography. The levels of siRNA uptake and targeted gene inhibition were detected in human lung cancer SPC-A1-GFP cells stably expressing green fluorescent protein. Examination of the cultured SPC-A1-GFP cells with fluorescent microscope and flow cytometry showed NPs loading Cy3-labeled siRNA had much higher intracellular siRNA delivery efficiencies than siRNA alone and Lipofectamine-siRNA complexes. The gene silencing efficiency of mPEG-PLGA-PLL NPs was higher than that of commercially available transfecting agent Lipofectamine while showing no cytotoxicity. Thus, the current study demonstrates that biodegradable NPs of mPEG-PLGA-PLL triblock copolymers can be potentially applied as novel non-viral vectors for improving siRNA delivery and gene silencing.     

Lipophilic 2′‐O‐Acetal Ester RNAs: Synthesis,Thermal Duplex Stability,Nuclease Resistance,Cellular Uptake,and siRNA Activity after Spontaneous Naked Delivery

The in vivo application of siRNA depends on its cellular uptake and intracellular release, and this is an unsatisfactorily resolved technical hurdle in medicinal applications. Promising concepts directed towards providing efficient cellular and intracellular delivery include lipophilic chemical modification of siRNA. Here we describe chemistry for the production of modified siRNAs designed to display improved transmembrane transport into human cells while preserving the potency of the RNAi‐based inhibitors. We report the synthesis and the biochemical and biophysical characteristics of 2′‐O‐phenylisobutyryloxymethyl (PiBuOM)‐modified siRNAs and their impact on biological activity. In the case of spontaneous cellular uptake of naked PiBuOM‐modified siRNA, we observed increased target suppression in human cells relative to unmodified or pivaloyloxymethyl (PivOM)‐modified siRNA. We provide evidence of improved spontaneous cellular uptake of naked PiBuOM‐modified siRNA and of substantial target suppression in human cells in serum‐containing medium.     

Preparation of CaCO3/polymer composite films via interaction of anionic starburst dendrimer with poly(ethylenimine)

Summary The CaCO₃/poly(ethylenimine) composite film was obtained in the presence of anionic poly(amidoamine) (PAMAM) dendrimer (G=3.5), whereas the formation of composite film was not observed without PAMAM dendrimer or with PAMAM dendrimer (G=1.5) judging from the results of scanning electron micrographs (SEM). The crystal phase of the CaCO₃ film formed was found to be calcite by FT-IR and XRD analysis. The adsorption of PAMAM dendrimer on poly(ethylenimine) film might cause local high concentration of calcium ion and induce a formation of the CaCO₃ film. Received: 23 October 2000/Accepted: 10 November 2000     

The use of poly(amidoamine) dendrimer in modification of jute for improving dyeing properties of reactive dyes

In this study, the poly(amidoamine) (PAMAM) G‐2 dendrimer was applied to the jute yarn. Fourier transform infrared spectrophotometry (FTIR) of the dendrimer‐treated jute yarn indicated that all carbonyl groups of the jute fiber have reacted with amino groups of the PAMAM dendrimer. Jute yarns which had been pretreated with PAMAM dendrimer displayed markedly enhanced color strength with reactive dyes, even when dyeing had been carried out in the absence of electrolyte or alkali. Dendrimer‐treated jute yarn showed much better light‐fastness than that of untreated jute yarn. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013