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Dendrimers are macromolecules with well-defined three-dimensional structures, sizes and surface charges. In this work, four generations of poly(amidoamine) (PAMAM) dendrimers were investigated at the micro-interface between two immiscible electrolyte solutions (μITIES) to understand their electrochemical responses as simple models of ionised macromolecules. Cyclic voltammetry (CV) across a range of aqueous phase pH revealed that all four generations (G0-G3) presented diffusion-controlled ion-transfer from aqueous to organic phase, while the reverse transfers from organic to aqueous phase varied with both pH and the dendrimer generation. The larger dendrimers (G2 and G3) show an adsorption behaviour at pH ≤ 3.5, but show a diffusional response at pH ≥ 6. On the other hand, the smaller dendrimers (G0 and G1) always show a diffusional response and are not impacted by the pH. This indicates that more highly charged dendrimers condense at the interface. The reverse scan of CVs showed that an increased applied potential was required to remove (desorb) these polycations from the interfaces in comparison to smaller, less charged species. Diffusion coefficients (D) were estimated, showing a decrease with increasing generation. Limits of detection for these dendrimers by CV at the μITIES were 0.4, 0.2, 0.7 and 0.5 μM for G0 to G3, respectively, while differential pulse voltammetry lowered the LODs (0.07, 0.05, 0.09 and 0.08 μM, respectively). These study shows that the μITIES provides a simple way to detect and evaluate the electrochemical behaviour of ionised macromolecules, providing a simple illustration of detection mechanism with diffusion or adsorption processes. [Display omitted] • Ionised PAMAM dendrimers are electroactive at liquid/liquid micro-interfaces. • Lower dendrimer generations show simple diffusion controlled behaviour. • Higher generations show adsorption behaviour on reverse CV sweeps. • Analytical sensitivity increases with generation number and decreasing pH. [ABSTRACT FROM AUTHOR]

Inspired by the distinctive merits of carbon nanoparticles (CNPs) and poly-(amidoamine) (PAMAM) dendrimers, we synthesized PAMAM modified CNPs (CNPs-PAMAM). First, CNPs were prepared using citrate acid and 1, 2, 4-triaminobenzene. Then, PAMAM was anchored on the surface of CNPs. The structure of PAMAM would remain unchanged under mild conditions of the postmodification method, making PAMAM retain its excellent drug carrying ability. Particularly, CNPs-PAMAM had exceptional optical properties of excitation-independent long wavelength emission. Excitation-independent emission can ensure the sensitivity of bioimaging. Long wavelength emission can avoid the autofluorescence interference of biological matrixes and have good tissue penetration. Further studies demonstrated that CNPs-PAMAM were able to electrostatically bind and condense small interfering RNA (siRNA) into stabilized nanocomplexes. The siRNA complexed with CNPs-PAMAM was endowed with an increased resistance against degradation and an enhanced cellular uptake. Moreover, CNPs-PAMAM-complexed siRNA targeting histone deacetylase 2 (HDAC2) could be effectively delivered into the neuron-like PC-12 cells, and exert its gene-silencing effect. Precisely inhibiting the so-called undruggable target HDAC2 opens a novel strategy for ischemic stroke treatment. Thus, CNPs-PAMAM offer a promising delivery carrier to unleash the siRNA's therapeutic potential. [ABSTRACT FROM AUTHOR]

Core-shell tecto dendrimers (CSTDs) are a kind of superstructured dendrimeric nanoconstructs with relatively high-generation dendrimers as the cores and low-generation dendrimers as the shells. Recently, there is growing evidence that the performance of CSTDs constructed with poly(amidoamine) (PAMAM) dendrimers of different generations as reactive modules is not only superior to that of single-generation dendrimers, but also overcomes some biomedical limitations (e.g., restricted drug loading capacity, limited tumor passive targeting based on enhanced permeability and retention effect) of single-generation dendrimers. Herein, the design of CSTDs for biological imaging, chemotherapy, gene therapy, and combination therapy are reviewed. The current challenges and future development prospects of CSTDs in the field of biomedicine are also analyzed.

Qing Hu,1,2,* Yifei Wang,1,* Lu Xu,1,* Dawei Chen,1,3 Lifang Cheng1 1Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People’s Republic of China; 2Department of Pharmaceutics, College of Pharmaceutical Sciences, Fujian Medical University, Fuzhou 350122, People’s Republic of China; 3School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lifang Cheng Email chenglifang0803@126.comIntroduction: A multifunctional redox- and pH-responsive polymeric drug delivery system is designed and investigated for targeted anticancer drug delivery to liver cancer.Methods: The nanocarrier (His-PAMAM-ss-PEG-Tf, HP-ss-PEG-Tf) is constructed based on generation 4 polyamidoamine dendrimer (G4 PAMAM). Optimized amount of histidine (His) residues is grafted on the surface of PAMAM to obtain enhanced pH-sensitivity and proton-buffering capacity. Disulfide bonds (ss) are introduced between PAMAM and PEG to reach accelerated intracellular drug release. Transferrin (Tf) was applied to achieve active tumor targeting. Doxorubicin (DOX) is loaded in the hydrophobic cavity of the nanocarrier to exert its anti-tumor effect.Results: The results obtained from in vitro and in vivo evaluation indicate that HP-ss-PEG-Tf/DOX complex has pH and redox dual-sensitive properties, and exhibit higher cellular uptake and cytotoxicity than the other control groups. Flow cytometry and confocal microscopy display internalization of HP-ss-PEG-Tf/DOX via clathrin mediated endocytosis and effective endosomal escape in HepG2 cancer cells. Additionally, cyanine 7 labeled HP-ss-PEG-Tf conjugate could quickly accumulate in the HepG2 tumor. Remarkably, HP-ss-PEG-Tf/DOX present superior anticancer activity, enhanced apoptotic activity and lower heart and kidney toxicity in vivo.Discussion: Thus, HP-ss-PEG-Tf is proved to be a promising candidate for effective targeting delivery of DOX into the tumor.Keywords: poly(amidoamine) dendrimers, histidine, transferrin, doxorubicin, pH and redox sensitivity

ObjectiveSecondary caries caused by oral microbiome dysbiosis and hybrid layer degradation are two important contributors to the poor resin–dentin bond durability. Cavity cleansers with long-term antimicrobial and anti-proteolytic activities are in demand for eliminating bacteria-induced secondary caries and preventing hybrid layers from degradation. The objectives of the present study were to examine the long-term antimicrobial effect and anti-proteolytic potential of poly(amidoamine) dendrimers with amino terminal groups (PAMAM-NH2) cavity cleanser.MethodsAdsorption tests by attenuated total reflectance–infrared (ATR-IR) spectroscopy and confocal laser scanning microscopy (CLSM) were first performed to evaluate whether the PAMAM-NH2 cavity cleanser had binding capacity to dentin surface to fulfill its relatively long-term antimicrobial and anti-proteolytic effects. For antibacterial testing, Streptococcus mutans, Actinomyces naeslundii, and Enterococcus faecalis were grown on dentin surfaces, prior to the application of cavity cleanser. Colony-forming unit (CFU) counts and live/dead bacterial staining were performed to assess antibacterial effects. Gelatinolytic activity within the hybrid layers was directly detected by in situ zymography. Adhesive permeability of bonded interface and microtensile bond strength were employed to assess whether the PAMAM-NH2 cavity cleanser adversely affected resin–dentin bonding. Finally, the cytotoxicity of PAMAM-NH2 was evaluated by the Cell Counting Kit-8 (CCK-8) assay.ResultsAdsorption tests demonstrated that the binding capacity of PAMAM-NH2 on dentin surface was much stronger than that of 2% chlorhexidine (CHX) because its binding was strong enough to resist phosphate-buffered saline (PBS) washing. Antibacterial testing indicated that PAMAM-NH2 significantly inhibited bacteria grown on the dentin discs as compared with the control group (p < 0.05), which was comparable with the antibacterial activity of 2% CHX (p > 0.05). Hybrid layers conditioned with PAMAM-NH2 showed significant decrease in gelatin activity as compared with the control group. Furthermore, PAMAM-NH2 pretreatment did not adversely affect resin–dentin bonding because it did not decrease adhesive permeability and microtensile strength. CCK-8 assay showed that PAMAM-NH2 had low cytotoxicity on human dental pulp cells (HDPCs) and L929.ConclusionsPAMAM-NH2 cavity cleanser developed in this study could provide simultaneous long-term antimicrobial and anti-proteolytic activities for eliminating secondary caries that result from a dysbiosis in the oral microbiome and for preventing hybrid layers from degradation due to its good binding capacity to dentin collagen matrix, which are crucial for the maintenance of resin–dentin bond durability.

Objective: Secondary caries caused by oral microbiome dysbiosis and hybrid layer degradation are two important contributors to the poor resin–dentin bond durability. Cavity cleansers with long-term antimicrobial and anti-proteolytic activities are in demand for eliminating bacteria-induced secondary caries and preventing hybrid layers from degradation. The objectives of the present study were to examine the long-term antimicrobial effect and anti-proteolytic potential of poly(amidoamine) dendrimers with amino terminal groups (PAMAM-NH2) cavity cleanser. Methods: Adsorption tests by attenuated total reflectance–infrared (ATR-IR) spectroscopy and confocal laser scanning microscopy (CLSM) were first performed to evaluate whether the PAMAM-NH2 cavity cleanser had binding capacity to dentin surface to fulfill its relatively long-term antimicrobial and anti-proteolytic effects. For antibacterial testing, Streptococcus mutans , Actinomyces naeslundii , and Enterococcus faecalis were grown on dentin surfaces, prior to the application of cavity cleanser. Colony-forming unit (CFU) counts and live/dead bacterial staining were performed to assess antibacterial effects. Gelatinolytic activity within the hybrid layers was directly detected by in situ zymography. Adhesive permeability of bonded interface and microtensile bond strength were employed to assess whether the PAMAM-NH2 cavity cleanser adversely affected resin–dentin bonding. Finally, the cytotoxicity of PAMAM-NH2 was evaluated by the Cell Counting Kit-8 (CCK-8) assay. Results: Adsorption tests demonstrated that the binding capacity of PAMAM-NH2 on dentin surface was much stronger than that of 2% chlorhexidine (CHX) because its binding was strong enough to resist phosphate-buffered saline (PBS) washing. Antibacterial testing indicated that PAMAM-NH2 significantly inhibited bacteria grown on the dentin discs as compared with the control group (p < 0.05), which was comparable with the antibacterial activity of 2% CHX (p > 0.05). Hybrid layers conditioned with PAMAM-NH2 showed significant decrease in gelatin activity as compared with the control group. Furthermore, PAMAM-NH2 pretreatment did not adversely affect resin–dentin bonding because it did not decrease adhesive permeability and microtensile strength. CCK-8 assay showed that PAMAM-NH2 had low cytotoxicity on human dental pulp cells (HDPCs) and L929. Conclusions: PAMAM-NH2 cavity cleanser developed in this study could provide simultaneous long-term antimicrobial and anti-proteolytic activities for eliminating secondary caries that result from a dysbiosis in the oral microbiome and for preventing hybrid layers from degradation due to its good binding capacity to dentin collagen matrix, which are crucial for the maintenance of resin–dentin bond durability. [ABSTRACT FROM AUTHOR]

The continued emergence of nanoscale materials for nanoparticle-based therapy, sensing and imaging, as well as their more general adoption in a broad range of industrial applications, has placed increasing demands on the ability to assess their interactions and impacts at a cellular and subcellular level, both in terms of potentially beneficial and detrimental effects. Notably, however, many such materials have been shown to interfere with conventional in vitro cellular assays that record only a single colorimetric end-point, challenging the ability to rapidly screen cytological responses. As an alternative, Raman microspectroscopy can spatially profile the biochemical content of cells, and any changes to it as a result of exogenous agents, such as toxicants or therapeutic agents, in a label free manner. In the confocal mode, analysis can be performed at a subcellular level. The technique has been employed to confirm the cellular uptake and subcellular localization of polystyrene nanoparticles (PSNPs), graphene and molybdenum disulfide micro/nano plates (MoS2), based on their respective characteristic spectroscopic signatures. In the case of PSNPs it was further employed to identify their local subcellular environment in endosomes, lysosomes and endoplasmic reticulum, while for MoS2 particles, it was employed to monitor subcellular degradation as a function of time. For amine functionalized PSNPs, the potential of Raman microspectroscopy to quantitatively characterize the dose and time dependent toxic responses has been explored, in a number of cell lines. Comparing the responses to those of poly (amidoamine) nanoscale polymeric dendrimers, differentiation of apoptotic and necrotic pathways based on the cellular spectroscopic responses was demonstrated. Drawing in particular from the experience of the authors, this paper details the progress to date in the development of applications of Raman microspectroscopy for in vitro, label free analysis of the uptake, fate and impacts of nanoparticle based materials, in vitro, and the prospects for the development of a routine, label free high content spectroscopic analysis technique.

Physicochemical characterization of polyamidoamine (PAMAM) dendrimers of generation 4.0 amine‐terminated (DG4.0) and 4.5 carboxy‐ended (DG4.5) was done. We have measured the pKa of the inner tertiary amine, the surface primary‐amine, and carboxyl‐terminal groups. We have conducted UV‐Vis absorption and fluorescence emission experiments as a function of pH. We have made a 4th derivative analysis of the UV‐Vis absorption experiments and compare the results with classical amide such as dimethylformamide. Our results have permitted us to calculate the pKa of the groups sensible to the pH in both dendrimers and compare the results with theoretical studies. On the one hand, the pKa values found for DG4.0 were 10.0±0.5 and 7.1±0.2, for primary and tertiary amines groups, respectively. On the other hand, the pKa values found for the DG4.5 were 3.5±0.7 and 6.8±0.4, for the carboxylic and tertiary amine groups. Our experimental results agree with theoretical ones. We offer probes that the dendrimers have two non‐traditional fluorophores, where one of them is the inner amide bond. The dendrimers show fluorescence emission in all the tested pH. [ABSTRACT FROM AUTHOR]

• The novel Fe3O4@PANI–PSS/PAMAM–QGO adsorbent was synthesized and characterized. • Extraction of PAHs compounds in environmental water samples. • The method exhibited satisfactory extraction recoveries for the MSPE. • The established method showed simple, rapid, reproducibility and good sensitivity. An efficient magneto–adsorbent composed of polyaniline blend poly(amidoamine) dendrimers modified graphene oxide quantum dots and magnetic Fe 3 O 4 particles (Fe 3 O 4 @PANI–PSS/PAMAM–QGO) for magnetic solid–phase extraction (MSPE) of polycyclic aromatic hydrocarbons (PAHs) in environmental water was synthesized. Fe 3 O 4 @PANI–PSS/PAMAM–QGO exhibited exceptional adsorption property for most PAHs analytes. The nanocomposite sorbent demonstrated a ferromagnetic behavior of 17.457 emu g−1, which is adequate for subsequent use in MSPE. Key parameters affecting the processes of adsorption and desorption, including the sorbent amount, vortex adsorption time, vortex extraction time, sample volume, a solvent for desorption and the solvent volume were all examined and optimized. The performance of MSPE using Fe 3 O 4 @PANI–PSS/PAMAM–QGO as adsorbent for four PAHs, including fluoranthene, acenaphthene, phenanthrene and pyrene were studied through high performance liquid chromatography equipped with spectrofluorometer. Under the optimal conditions, Fe 3 O 4 @PANI–PSS/PAMAM–QGO showed a wide linearity of 10–1,000 ng mL−1, low detection limit (LOD) ranging from 1.92 to 4.25 ng mL -1 and high accuracy (recoveries of 93.6–96.5 %). Enrichment factors up to 185 were achieved. Furthermore, Fe 3 O 4 @PANI–PSS/PAMAM–QGO exhibited good recyclability (10 times, RSDs ≤ 5.35%), while maintaining its high efficiency in the extraction of PAHs. The proposed method was successfully applied for environmental samples. Recoveries ranging from 81.2 to 106.2 % were obtained, indicating a low matrix effect and the robustness of the optimized MSPE method. Based on these features and under the optimal extraction conditions, Fe 3 O 4 @PANI–PSS/PAMAM–QGO was demonstrated to be a successful tool for the rapid and sensitive extraction of PAHs in the samples. [ABSTRACT FROM AUTHOR]

Abstract: Nowadays, antibiotic abuse increases the emergence of multidrug‐resistant bacterial strains, which is the major reason for the failure of conventional antibiotic therapies. Therefore, developing novel antibacterial materials or therapies is an urgent demand. In the present study, photothermal and NO‐releasing properties are integrated into a single nanocomposite to realize more efficient bactericidal effects. To this end, polydopamine (PDA) coated iron oxide nanocomposite (Fe3O4@PDA) is used as a photoconversion agent and the core, first three generation dendritic poly(amidoamine) (PAMAM‐G3) is grafted on the surface of Fe3O4@PDA, and subsequently NO is loaded with the formation of NONOate. The resultant Fe3O4@PDA@PAMAM@NONOate displays controllable NO release property under intermittent 808 nm laser irradiation and excellent bacteria‐separation efficiency. Moreover, excellent synergistic photothermal and NO antibacterial effects are observed against both Gram‐negative Escherichia coli and Gram‐positive Staphylococcus aureus, where bacterial viability and biofilm are significantly reduced. An antibacterial mechanism study reveals that the materials first adsorb onto the bacterial membrane, then cause damage to the membrane by the increased local temperature and the released NO under laser irradiation conditions, finally leak the intracellular components like DNA and induce bacteria death. The work provides a novel way for designing of antibacterial materials with higher efficiency. [ABSTRACT FROM AUTHOR]

In this work, a novel non-enzymatic superoxide anion (O 2 • − ) sensor was constructed based on Ag nanoparticles (NPs) / poly (amidoamine) (PAMAM) dendrimers and used to investigate the dynamic process of O 2 • − release from living cells. The AgNPs/PAMAM nanohybrids were characterized by transmission electron microscopy (TEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The fabricated electrode exhibited excellent catalytic activity toward the reaction of O 2 • − with a super low detection limit (LOD) of 2.530 × 10 –13 M (S/N = 3) and wide linear range of 8 orders of magnitude. It could fulfill the requirement of real-time measurement O 2 • − released from living cells. Furthermore, zymosan was chosen as the stimulant to induce O 2 • − generation from cancer cells (rat adrenal medulla pheochromocytoma cell (PC12)). The electrochemical experiment results indicated that the levels of intracellular O 2 • − depended on the amount of Zymosan. A large amount of O 2 • − generated in the living cells by added heavy stimulant could damage cells seriously. More importantly, a vitro simulation experiment confirmed the role of superoxide dismutase (SOD) for the first time because it could maintain the O 2 • − concentration at a normal physiological range. These findings are of great significance for evaluating the metabolic processes of O 2 • − in the biological system, and this work has the tremendous potential application in clinical diagnostics to assess oxidative stress. [ABSTRACT FROM AUTHOR]

Cyanine dyes are promising candidates in biomedical applications. Although various delivery systems have been developed to enhance their properties, their dendrimer-based delivery systems are seldom investigated. Herein, amine-terminated generation 5 poly(amidoamine) (G5.NH2) dendrimers and new indocyanine green (IR820) dyes were chosen as models to study the loading ability of dendrimers for cyanine dynes. G5.NH2 dendrimers were pre-modified with arginine-glycine-aspartic (RGD) peptides, poly(ethylene glycol) chains, and acetyl groups to be endowed with cancer cell specificity and biocompatibility. The formed Ac-PR dendrimers were used to load IR820, followed by thorough characterization. The loaded number of IR820 was estimated to be 6.7 per dendrimer. The stability of IR820 was improved through dendrimer loading, which was proved by their UV-vis spectra under different kinds of storage conditions. In addition, the formed Ac-PR dendrimers can retain the loaded IR820 effectively. Their cytocompatibility was desirable under the studied conditions. Their cellular uptake behaviors were demonstrated to be enhanced by RGD modification, showing concentration-, co-incubation time-, and αvβ3 integrin receptor-dependent properties, displaying a cytoplasm-location. The findings from this work demonstrated the versatile loading and delivery capacity of dendrimers for near-infrared (NIR) dyes, providing fundamental data for the development of dendrimer/NIR dye systems for biomedical applications, especially for cancer theranostic applications.

The overuse of antibiotics has resulted in severe environmental pollution. Most conventional techniques for antibiotic detection are time-consuming, professional operator-dependent and require expensive instruments. Herein, we describe a simple optoelectronic tongue consisting of three elaborately designed fifth-generation PAMAMs (PF1-PF3) to achieve rapid detection of antibiotics. 19 antibiotics were rapidly and accurately differentiated in water with 97% accuracy via this minimal tongue, proving the rationality of the array's design. Furthermore, this tongue enabled the parallel detection of multiple sulfonamide residues (0.05 mM) in milk samples with 100% accuracy, demonstrating robust real sample detection capability. In this strategy, we have provided an efficient way for the comprehensive identification and determination of antibiotics. [Display omitted] • A chemical tongue was constructed based on functionalized poly(amidoamine) dendrimers. • Poly(amidoamine) dendrimers were modified with elaborately designed substituents and fluorophores. • The sensor array identified 19 antibiotics in water by linear discriminant analysis. • The sensor array successfully identified antibiotics of various concentrations and mixing ratios. • Sulfonamide antibiotics were well distinguished in the complicated environment of milk. [ABSTRACT FROM AUTHOR]

Despite the expected increase of nanotechnology applications, limited information is currently available on the occurrence, fate and negative impact of engineered nanosized particles in the environment. Plants are an integral and essential part of the ecosystems and their response to nanomaterials exposure is therefore of great interest. In this work, different parameters including root growth, mitotic index and chromosome aberrations were used to estimate the potential ecotoxicity of low generation (G3) hydroxyl- and amine-terminated poly(amidoamine) dendrimers using the Allium cepa test. The findings of the present study indicate that both tested dendrimers produce toxic effects in a higher plant system. The analysis of macroscopic parameters, used in testing for general toxicity, revealed reduction of mean root length in bulbs exposed to high concentrations. In parallel, we observed a decrease in the mitotic activity of root meristems which was associated with severe defects in chromosome segregation. Our results may greatly contribute to characterize the toxicological profile and risk of these potentially emerging pollutants in the environment. [ABSTRACT FROM AUTHOR]

To solve the contradiction between long circulation time and effective intracellular drug release, redox and pH-responsive drug delivery system was developed by incorporated redox-sensitive disulfide linkage between poly(amidoamine) dendrimers (PAMAM) and poly(ethylene glycol) (PEG). Doxorubicin (DOX) was loaded into the hydrophobic core of the conjugates to prepare PAMAM-SS-PEG/DOX complexes (PSSP/DOX). In vitro release studies suggested that DOX release from PSSP/DOX complexes followed an redox and acid-triggered manner and increased with increasing PEGylation degree. In vitro cytotoxicity of PSSP/DOX complexes against B16 tumor cells increased with, while cellular uptake decreased with increasing PEGylation degree. Further, intracellular DOX release observation and measurement indicate that the intracellular DOX release played a critical role for the cytotoxicity of DOX-loaded PSSP conjugates. In addition, cellular entry mechanism of the PSSP/DOX study demonstrated that both clathrin- and caveolae-mediated endocytosis were the primary pathways for cellular entry of PSSP/DOX. Finally, in vivo study of PSSP/DOX complexes in B16 tumor-bearing mice indicate that PSSP/DOX could significantly improve antitumor efficiency and present a good safety. The redox and pH-responsive drug delivery system has been demonstrated to be a promising candidate for solid tumor therapy. Statement of Significance In previous research, pH-sensitive diblock polymer of poly(ethylene glycol)-poly(2,4,6-trimethoxybenzylidene-pentaerythritol carbonate) (PEG-PTMBPEC) was synthesized to facilitate the intracellular anticancer drug release. However, the nanoparticles based on PEG-PTMBPEC get into the tumor cells just relying on the EPR-mediated passive targeting resulting in the low drug accumulation. Therefore, cRGD peptide modified PEG-PTMBPEC polymeric micelles were developed for specific targeted delivery of doxorubicin (DOX) to neovascular cells and tumor cells simultaneously. The precise intracellular target site and effective drug concentration will contribute to enhancing the antitumor toxicity and reducing the systematic toxicity of DOX. The cRGD modified pH-sensitive micellar system is a promising vehicle for intracellular drug delivery to αvβ3 integrin receptor overexpressed tumor cells and neovascular cells. [ABSTRACT FROM AUTHOR]

An ultrasensitive sandwich-type electrochemiluminescent biosensor based on carbonaceous based nanomaterials was fabricated for alpha-fetoprotein detection. Herein, the composite of fullerene, graphene oxide and chitosan with specific surface area, good water dispersibility, and excellent biocompatibility was first modified onto the electrode surface and then it was in situ electrochemical reduced to improve the conductivity. After the capturing antibody was immobilized onto the modified electrode surface, the detection antibody together with poly(amidoamine) dendrimers functionalized carbon nanodots as the recognizable signal tags was self-assembled onto the electrode by typical sandwich immune reaction. By this design, the abundant functional groups, good water dispersibility and good electroconductivity of poly(amidoamine) dendrimers functionalized carbon nanodots make the composite not only an immobilizing platform to carrier numerous detection antibodies, but also an promising promoter for the electrochemiluminescent signal of luminol. With the aforementioned amplify factor, the established electrochemiluminescent biosensor under the optimal conditions demonstrated a wider dynamic response from 1 fg mL −1 to 80 ng mL −1 with a low detection limit of 0.33 fg mL −1 . Additionally, the experimental results exhibited the immunosensor possessed excellent stability, reproducibility and selectively. Accordingly, this immunosensing strategy for alpha-fetoprotein with the assistance of poly(amidoamine) dendrimers functionalized carbon nanodots provided a promising approach in clinical disease scanning. [ABSTRACT FROM AUTHOR]

The article presents a study that evaluates whether GlcNPAMAM exerts inhibitory effect on IL-8 production by H. pylori in gastric epithelial cells. The study is undertaken through obtaining carboxylic acid-terminated generation 3.5 PAMAM dendrimers (G3.5-PAMAM) and D-(+)-glucosamine hydrochloride (GlcN) and the removal of methanol through evaporation. The results of the study indicate that there is an exertion of inhibitory effects of the said mixture

Osteoporosis is an age-related metabolic disease of bone, resulting in bone pain and even bone fragility and brittle fracture. Inhibiting overactive osteoclasts while promoting osteoblast activity is an ideal way to treat osteoporosis. Previous studies have demonstrated that natural compounds, such as curcumin (Cur) have dual roles both in promoting bone formation and inhibiting bone resorption, making them promising candidates for osteoporosis treatment. However, their poor water solubility, high dosage of curative effect and significant toxicity to other organs have largely limited their clinical translations. In this study, a novel method was reported to conjugate Cur and poly(amidoamine) dendrimers (PAD) using hexachlorocyclotriphosphazene (HCCP) as the linkage through a one-pot reaction, forming stable and uniform Cur loaded nanospheres (HCCP-Cur-PAD, HCP NPs). Owing to the hydrophilicity of PAD and hydrophobicity of Cur, HCP NPs can self-assemble into nanoparticles with particle size of 138.8 ± 78.7 nm and display excellent water dispersity. The loading capacity of Cur can reach 27.2% and it can be released from HCP NPs with pH-responsiveness. In vitro experimental results demonstrated that the HCP NPs entered lysosomes by endocytosis and proved dual anti-osteoporosis effects of inhibiting osteoclasts and promoting osteoblasts. [Display omitted] • Curcumin-containing poly(amidoamine) dendrimers were synthesized via a one-pot reaction. • The poor water dispersion of curcumin was overcome via conjugation with poly(amidoamine). • HCCP-Cur-PAD displays pH-controlled drug release behavior for osteoporosis treatment. • Hexachlorocyclotriphosphazene was used as the bridge for curcumin and poly(amidoamine). [ABSTRACT FROM AUTHOR]

Two cationic gemini surfactants and two generations of poly(amidoamine) (PAMAM) dendrimers ( G = −0.5 and G = 0.5) were studied as retarders in acrylic dyeing with a cationic dye. Effects of retarder concentrations, dyeing time, and temperature were investigated by means of UV–Vis spectrophotometry. The results indicated that the dye adsorption decreased in the presence of the species and more uniform dyeing was achieved. The PAMAM dendrimers had lower retarding action than the cationic gemini surfactants which was attributed to their non-permanent and lower cationic charge density. Kinetics of the dyeing systems were also evaluated by four different empirical models. The modified Cegarra-Puente model fitted the dyeing kinetic data somewhat better than the other empirical kinetic models. Moreover, the activation energy of the dyeing systems was calculated and reported. [ABSTRACT FROM AUTHOR]

Poly(amidoamine) dendrimers (PAMAM) are polymeric macromolecules that can find their use as carriers of small ligand molecules such as cosmetics and drugs. 5- Fluorouracil is a potent oncological drug, whose usage is limited because of its relatively high toxicity.The surface and internal layer groups in PAMAM dendrimer belonging to the third (G3) generation create an open-type structure, which facilitate small ligand molecules to bind with them.The formation equilibrium of PAMAM G3 dendrimer complex with an oncologic drug such as 5 fluorouracil (FU) in water at room temperature was examined. Using the results of the drug solubility in dendrimer solutions, the maximal number of drug molecules in the dendrimer-drug complex was evaluated. Solubility results show that PAMAM G3 dendrimer can transfer tens 5 fluorouracil molecules in aqueous solution.This research work was funded from the Polish budget appropriations for science in the years 2013-2015, project number IP2012 022372.

Poly(amidoamine) dendrimers are very interesting macromolecules with highly branched structures and globular-shaped branched polymeric architectures. They are widely used for drug and gene delivery applications. In order to provide important insight into the interactions of poly(amidoamine) dendrimers with some organic acceptors, the binding of small molecules to 4-hexylamino-1,8-naphthalimide-labelled PAMAM dendrimer (PD) have been studied by spectrophotomeric method. The acceptors used in this research include chloranilic acid (CLA),p-chloranil (CHL), 2,6-dichloroquinone-4-chloroimide (DCQ), 2,6-dibromoquinone-4-chloroimide (DBQ), 7,7ʹ,8,8ʹ-tetracyanoquinodimethane (TCNQ), picric acid (PA), 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and iodine monobromide (IBr). The spectrophotometric measurements proved that all the charge-transfer (CT) complexes are formed via a stoichiometry (PD: acceptor) of 1:2 (except for IBr acceptor). Accordingly the obtained complexes could be formulated as [(PD)(CLA)2], [(PD)(DCQ)2], [(PD)(DBQ)2], [(PD)(TCNQ)2], [(PD)(PA)2], [(PD)(CHL)2], [(PD)(DDQ)2] and [(PD)(IBr)4]. Benesi–Hildebrand and its modification methods were applied to estimate the spectroscopic and physical data. [ABSTRACT FROM PUBLISHER]

Taxanes are the most effective, efficient and broad spectrum anticancer drugs for the treatment of various cancers. However, poor aqueous solubility is the major problem in their delivery at higher concentrations in cancer cells. In this research work, poor solubility of taxanes is addressed by preparing dendrimer and d -α-tocopherol polyethylene glycol succinate (TPGS) mixed micelles by taking into consideration the advantages of TPGS such as solubility enhancement and P -glycoprotein inhibition. Dendrimer–TPGS mixed micelles were prepared by solvent casting method. Docetaxel (DTX) and paclitaxel (PTX) were chosen as model drugs representing the group of taxanes. Nanomicelles were characterized by DLS, FTIR, PXRD, in vitro drug release and hemolytic studies. Effects of pH and dendrimer to TPGS ratio on the solubility of taxanes were also studied. Solubility of DTX and PTX were increased by 20.36 and 34.95 folds, respectively, when formulated in dendrimer–TPGS mixed micelles. Drug release studies exhibited better release profile of encapsulated drug at acidic pH which is advantageous in enhanced intracellular drug release in cancer cells. Formulations were found to be biocompatible in hemolytic toxicity assay. Cytotoxicity studies revealed that anticancer activities of both drugs were enhanced after encapsulation in micelles against cancer cells while caused very low toxicity to normal cells. Thus, dendrimer–TPGS mixed micelles are promising alternate for delivery of poorly water-soluble drugs taxanes. [ABSTRACT FROM AUTHOR]

Carboxymethylchitosan/poly(amidoamine) (CMCht/PAMAM) dendrimer nanoparticles, comprised of a PAMAM dendrimer core grafted with chains of CMCht, have recently been proposed for intracellular drug delivery. In previous reports, these nanoparticles had lower levels of cytotoxicity when compared with traditional dendrimers. In this study, the short-term in vivo biodistribution of fluorescein isothiocyanate (FITC)-labeled CMCht/PAMAM dendrimer nanoparticles after intravenous (IV) injections in Wistar Han rats was determined. The brain, liver, kidney, and lung were collected at 24, 48, and 72 h after injection and stained with phalloidin–tetramethylrhodamine isothiocyanate (TRITC, red) and 4′,6-diamidino-2-phenylindole dihydrochloride (DAPI, blue) to trace the nanoparticles within these tissues. The liver, kidney, and lung were also stained for hematoxylin and eosin to assess any morphological alterations of these organs. CMCht/PAMAM dendrimer nanoparticles were observed within the vascular space and parenchyma of liver, kidney, and lung and in the choroid plexus, after each injection period. No particles were observed in the brain parenchyma, nor any apparent deleterious histological changes were observed within these organs. The CMCht/PAMAM dendrimer nanoparticles were stable in circulation for a period of up to 72 h, targeting the main organs/systems through internalization by the cells present in their parenchyma. These results provide positive indicators to their potential use in the future as intracellular drug delivery systems. [ABSTRACT FROM AUTHOR]

Abstract: Risperidone is an approved antipsychotic drug belonging to the chemical class of benzisoxazole. This drug has low solubility in aqueous medium and poor bioavailability due to extensive first-pass metabolism and high protein binding (>90%). As new strategies to improve treatments efficiency are needed, we have studied cationic G4 PAMAM dendrimers’ performance to act as efficient nanocarriers for this therapeutic drug. In this respect, we explored dendrimer–risperidone complexation dependence on solvent, temperature, pH and salt concentration, as well as in vitro cytotoxicity measured on L929 cell line and human red blood cells. The best dendrimer–risperidone incorporation was achieved when a mixture of 70:30 and 90:10 v/v chloroform:methanol was used, obtaining 17 and 32 risperidone molecules per dendrimer, respectively. No cytotoxicity on L929 cells was found when dendrimer concentration was below 3 × 10−2 μM and risperidone concentration below 5.1 μM. Also, no significant hemolysis or morphological changes were observed on human red blood cells. Finally, attempting to obtain an efficient drug delivery system for risperidone, incorporation in G4 PAMAM dendrimers was optimized, improving drug solubility with low cytotoxicity. [Copyright &y& Elsevier]

Abstract: A new family of gene delivery vectors is synthesized consisting of a medium-size generation PAMAM dendrimer (generation 5, with amine termini) core randomly linked at the periphery to hydrophobic chains that vary in length (12 to 16 carbon alkyl chains) and number (from 4.2 to 9.7 in average). The idea subjacent to the present work is to join the advantages of the cationic nature of the dendrimer with the capacity of lipids to interact with biological membranes. Unlike other amphiphilic systems designed for the same purpose, where the hydrophobic and hydrophilic moieties coexist in opposite sides, the present vectors have a hydrophilic interior and a hydrophobic corona. The vectors are characterized in respect to their ability to neutralize, bind and compact plasmid DNA (pDNA). The complexes formed between the vectors and pDNA are analyzed concerning their size, ζ-potential, resistance to serum nucleases, capacity of being internalized by cells and transfection efficiency. These new vectors show a remarkable capacity for mediating the internalization of pDNA with minimum cytotoxicity, being this effect positively correlated with the –CH2– content present in the hydrophobic corona. Gene expression in MSCs, a cell type with relevancy in the regenerative medicine clinical context, is also enhanced using the new vectors but, in this case, the higher efficiency is shown by the vectors containing the smallest hydrophobic chains. [Copyright &y& Elsevier]

Poly(amidoamine) (PAMAM) dendrimers are widely used in medical applications. However, dendrimers bearing positively charged surface groups are prone to destabilize cell membrane and cause cell lysis. The lytic effect of dendrimers on red blood cells (RBCs) namely hemolysis is extremely dangerous when administered in vivo. To diminish the hematologic toxicity, we modified PAMAM dendrimers with poly(ethylene glycol) (PEG) of three molecular weights (2k, 5k, and 20k). The protective effect of PEGylation against PAMAM dendrimer‐induced hemolysis was studied. RBCs morphology and surface structure were analyzed by optical microscopy (OM) and atomic force microscopy (AFM). The results indicated that PAMAM and PEG‐2k modified dendrimers induced hemolysis at 0.1 and 0.5 mg/mL respectively, whereas PEG‐5k and PEG‐20k modified dendrimers showed no significant difference in hemolysis compared with control even at 5 mg/mL. OM and AFM investigation indicated PAMAM and PEG‐2k modified dendrimers caused RBCs aggregation and lysis. However, no changes were observed in the overall shape of RBCs treated with PEG‐5k and PEG‐20k modified dendrimers. The surface roughness of RBCs treated with PEGylated dendrimers were far lower than that of RBCs treated with PAMAM dendrimers. This study demonstrated that hemocompatibility of PAMAM dendrimers could be greatly enhanced by PEGylation. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010 [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this work was to assess the impact of PEGylation on transepithelial transport of anionic poly(amidoamine) dendrimers. Cytotoxicity, uptake and transport across Caco-2 cells of PEGylated G3.5 and G4.5 PAMAM dendrimers were studied. Methoxy polyethylene glycol (750 Da) was conjugated to carboxylic acid-terminated PAMAM dendrimers at feed ratios of 1, 2 and 4 PEG per dendrimer. Compared to the control, PEGylation of anionic dendrimers did not significantly alter cytotoxicity up to a concentration of 0.1 mM. PEGylation of G3.5 dendrimers significantly decreased cellular uptake and transepithelial transport while PEGylation of G4.5 dendrimers led to a significant increase in uptake, but also a significant decrease in transport. Dendrimer PEGylation reduced the opening of tight junctions as evidenced by confocal microscopy techniques. Modulation of the tight junctional complex correlated well with changes in PEGylated dendrimer transport and suggests that anionic dendrimers are transported primarily through the paracellular route. PEGylated dendrimers show promise in oral delivery applications where increased functionality for drug conjugation and release is desired. [Copyright &y& Elsevier]

This study was performed to investigate the simultaneous detection of carmoisine and tartrazine, two food azo dyes, with a new voltammetric sensor based on graphene oxide-Fe 3 O 4 (GO-Fe 3 O 4) nanocomposite functionalized with fourth-generation poly(amidoamine) (G4 PAMAM) dendrimers (GO-Fe 3 O 4 -G4 PAMAM) and ionic liquid (IL) modified carbon paste electrode (GO-Fe 3 O 4 -G4 PAMAM/ILCPE). The GO-Fe 3 O 4 -G4 PAMAM was synthesized and characterized by X-ray diffraction (XRD), field emission-scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDX), vibrating-sample magnetometer (VSM), and fourier transform infrared (FT-IR) techniques. Cyclic voltammetry (CV) was used to evaluate the electrochemical behavior of carmoisine , revealing the good electrocatalytic function of GO-Fe 3 O 4 -G4 PAMAM/ILCPE. Linear response from 0.1 to 170.0 μM was obtained based on carmoisine electrochemical oxidation through differential pulse voltammetry (DPV). The limit of detection (LOD) value obtained was 0.02 μM. Also, the GO-Fe 3 O 4 -G4 PAMAM/ILCPE was used for the simultaneous determination of carmoisine and tartrazine. In co-existence system containing carmoisine and tartrazine, the developed sensor exhibited well-defined and separate DPV peaks (i.e., 770 mV) for carmoisine and tartrazine. Besides, repeatability, reproducibility and stability studies were performed. Additionally, the analytical application of this sensor was demonstrated by determination of carmoisine and tartrazine in food samples including lemon juice and powdered juice. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Camptothecin (CPT), a plant alkaloid isolated from Camptotheca acuminata, has an extremely low solubility in aqueous medium, which presents a major challenge during drug formulation in clinical trails. In the present study we investigated the potential of poly(amidoamine) (PAMAM) dendrimers as drug carriers of CPT through aqueous solubility studies. Results showed that the aqueous solubility of CPT was significantly increased by PAMAM dendrimers. The effect of PAMAM generation on CPT solubility was also evaluated. These studies indicated that PAMAM dendrimers might be considered as biocompatible carriers of CPT. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: The intermolecular charge-transfer (CT) complexes formed between two poly(amidoamine) dendrimers (PAMAM) from zero (D1) and second generation (D2) as donor and iodine as σ-acceptor have been studied spectrophotometrically in the chloroform medium. The suggested structures of the solid iodine charge-transfer complexes investigated by several techniques using elemental analysis, mid infrared spectra, and thermal analysis (TGA and DTG) of the solid CT-complexes along with the photometric titration curves for the reactions. The results indicate the formation of two CT-complexes [(D1)]–I2 and [(D2)]–2I2 with acceptor:donor molar ratios of 1:1 and 1:2, respectively. The kinetic parameters (non-isothermal method) for their decomposition have been evaluated by graphical methods using the equations of Horowitz–Metzger (HM) and Coats–Redfern (CR). [Copyright &y& Elsevier]

Abstract: Protein-resistant films derived from the fifth-generation poly(amidoamine) dendrimers (PAMAM G5) functionalized with oligo(ethylene glycol) (OEG) derivatives consisting of various ethylene glycol units (EG n , , 4, and 6) were prepared on the self-assembled monolayers (SAMs) of 11-mercaptoundecanoic acid (MUA) on gold substrates. The resulting films were characterized by ellipsometry, contact angle goniometry, and X-ray photoelectron spectroscopy (XPS). About 35% of the peripheral amines of the dendrimers were reacted with N−hydroxysuccinimide-terminated EG n derivatives (NHS-EG n ). The dendrimer films showed improved stability over octadecanethiolate SAMs on gold in hot solvents, attributed to the formation of multiple amide bonds per PAMAM unit with underlying NHS-activated MUA monolayer. The EG n -attached PAMAM surfaces with reduced the adsorption of fibrinogen to ∼20% monolayer, whereas 2–3% for or 6. The dendrimer films with various densities of EG n molecules on PAMAM surfaces were prepared by immersion of the NHS-terminated MUA-functionalized gold substrates in ethanolic solutions containing PAMAM and NHS-EG n of various mole ratios. The density (r) of the EG n molecules on the PAMAM surfaces is consistent with the mole ratio () of NHS-EG n /free amine of PAMAM in solutions. The resistance to protein adsorption of the resulting surfaces is correlated with the surface density and the length of the EG chains. At their respective r, the EG n -modified dendrimer films resisted ∼95% adsorption of fibrinogen on gold surfaces. Finally, the specific binding of avidin to the ∼5% and ∼40% biotinylated EG3 dendrimers (surface density of biotin with respect to the total number of terminal amino groups on PAMAM G5) gave rise to about 50% and 100% surface coverage by avidin, respectively. [Copyright &y& Elsevier]

The interactions of amino-terminated, and ethylenediamine core poly(amidoamine) (PAMAM) dendrimers and their derivatives with bovine serum albumin (BSA) were investigated by fluorescence spectroscopy. Experimental results showed that the fluorescence intensity of BSA decreased after the addition of different modified dendrimers, and the extent of the fluorescence quenching caused by various modified dendrimers strongly depends upon the different functional groups on their surfaces. We also investigated the influence of pH and ionic strength on the interaction between various modified dendrimers and BSA. Circular dichroism (CD) spectroscopic measurements showed that the content of u-helix structure of BSA decreased after the addition of different modified dendrimers, which indicated that dendrimers induced changes in the secondary structure of BSA. [ABSTRACT FROM AUTHOR]

The interaction between amino-terminated, and ethylenediamine core poly(amidoamine) (PAMAM) dendrimers and herring sperm DNA was investigated by various spectroscopic methods including UV spectroscopy, fluorescence spectroscopy, microscopic FTIR- and circular dichroism (CD-) spectroscopy. Ethidium bromide (EB) is used as a nucleic acid probe for this study. Experimental results show that PAMAM dendrimers can form stable complexes with DNA and the dendrimers bind to DNA sufficiently strong which cannot be displaced by EB, and we also found that the formation of the complexes can cause the conformation change of the DNA secondary structure. According to the Scatchard analysis, the association constant of PAMAM to DNA is calculated to be 2.53 ⊗ 104 mol/L-1. [ABSTRACT FROM AUTHOR]

Abstract: The atomic force microscopy (AFM) and transmission electron microscopy (TEM) have been performed on the poly(amidoamine) dendrimers of second generation (2G) and its fluoroderivative (2D) at room temperature. Both studies have demonstrated that 2G and 2D exist in large aggregates on solid surface. The presence of ionic surfactants facilitates their solubilization in micellar phase resulting in the aggregates of much smaller dimensions. The aqueous bulk properties of 2G and 2D both in the absence as well as in the presence of ionic surfactants (i.e. dodecyltrimethylammonium bromide (DTAB), dimethylene bis (dodecyldimethylammonium bromide) (12-2-12), and sodium dodecyl sulfate (SDS)) have been carried out with the help of pyrene fluorescence and turbidity (τ) measurements. From the variation of I 1/I 3 pyrene intensity and the τ of these aqueous solutions, it has been found that both DTAB and 12-2-12 interact with the surface groups of 2G and 2D favorably in basic medium, while SDS has been found to interact with that in acidic medium. Apart from this, interactions of cationic surfactants have been found to be stronger with 2D in comparison to 2G, while reverse has been observed in the case of SDS. [Copyright &y& Elsevier]

Abstract: The pyrene fluorescence measurements have been carried out for the micelle formation of sodium dodecyl sulfate (SDS), dodecyltrimethylammonium bromide (DTAB), and dimethylene bis(dodecyldimethylammonium bromide) (12-2-12) in the presence of fixed different amounts of various generations of poly(amidoamine) (PAMAM). The critical micelle concentration (cmc) of SDS decreases with an increase in the fixed amount of PAMAM, suggesting the facilitation of micellization due to the participation of SDS–PAMAM complex in the micelle formation. This behavior has not been observed for DTAB/12-2-12 in the presence of various generations of PAMAM. The results indicate that SDS always has stronger interactions with all the generations of PAMAM in comparison to those of DTAB and 12-2-12. [Copyright &y& Elsevier]

Abstract: The purpose of this study was to determine the influence of a controlled incremental increase in size, molecular weight and number of amine, carboxylate and hydroxyl surface groups in several series of poly(amidoamine) (PAMAM) dendrimers for controlled ocular drug delivery. The duration of residence time was evaluated after solubilization of several series of PAMAM dendrimers (generations 1.5 and 2–3.5 and 4) in buffered phosphate solutions containing 2‰ (w/v) of fluorescein. The New Zealand albino rabbit was used as an in vivo model for qualitative and quantitative assessment of ocular tolerance and retention time after a single application of 25 μl of dendrimer solution to the eye. The same model was also used to determine the prolonged miotic or mydriatic activities of dendrimer solutions, some containing pilocarpine nitrate and some tropicamide, respectively. Residence time was longer for the solutions containing dendrimers with carboxylic and hydroxyl surface groups. No prolongation of remanence time was observed when dendrimer concentration (0.25–2%) increased. The remanence time of PAMAM dendrimer solutions on the cornea showed size and molecular weight dependency. This study allowed novel macromolecular carriers to be designed with prolonged drug residence time for the ophthalmic route. [Copyright &y& Elsevier]

Some novel fluorescent poly(amidoamine) dendrimers supported by a polyamide-6 matrix have been prepared and studied for the first time. The colour characteristics of the novel materials have been determined and found to be dependent on the nature of 1,8-naphthalimides bonded to their periphery amino groups. The materials have been treated with protons and cuprum cations. The resulting into changes in the colour characteristics and photostability of the dendrimers has been investigated. It has been shown that these ions inhibit the photodegradation of dendrimers molecules studied. [Copyright &y& Elsevier]

Construction of organic-inorganic hybrid materials with controlled mineralization analogous to those produced by nature is now a current interest for both organic and inorganic chemists to have an understanding of the mechanism of the natural biomineralization process, as well as to seek industrial and technological applications. Model systems, in which low-molecular-weight, linear polymeric materials have been used to study the effect of molecular properties such as charge and functionality on inorganic crystallization, are providing insights into the possible mechanisms operating in biology. Due to the unique and well-defined secondary structures of the dendrimers, anionic dendrimers should be a good candidate for studying inorganic crystallization. This paper provides a general survey of recent research on crystal nucleation and growth of calcium carbonate by poly(amidoamine) (PAMAM) dendrimers with carboxylate groups at the external surfaces. To cite this article: K. Naka, Y. Chujo, C. R. Chimie 6 (2003). [Copyright &y& Elsevier]

Generations 0 through 5 of ethylenediamine-core poly(amidoamine) dendrimers were synthesized and capillary zone electrophoresis has been applied to the separation of different generations of synthesized dendrimers and for the characterization of individual generations. [Copyright &y& Elsevier]

Purpose. To study the influence of a controlled incremental increase in size and molecular weight of a series of poly(amidoamine) (PAMAM) dendrimers on their extravasation across the microvascular network endothelium. Methods. A series of PAMAM dendrimers (generations 0-4) were fluorescently labeled using fluorescein isothiocyanate (FITC). Purification and fractionation of the fluorescently labeled polymers were done using size exclusion chromatography. The hamster cremaster muscle preparation was used as an in vivo model to study the extravasation process of the fluorescently labeled polymers. The extravasation process was visualized and recorded using intravital microscopy techniques. Analysis of the recorded experiments was done using Metamorph Imaging System. Extravasation of the fluorescently labeled polymers is reported in terms of their extravasation time (τ), i.e., the time needed for the fluorescence intensity in the interstitial tissue to reach 90% of the fluorescence intensity in the neighboring microvessels. Results. Extravasation time (τ) describes the rate of microvascular extravasation of polymeric drug carriers across the microvascular endothelium into the interstitial tissue. Extravasation time (τ) of the studied PAMAM dendrimers showed size and molecular weight dependence. An increase in size and/or molecular weight of PAMAM dendrimers resulted in a corresponding exponential increase in the extravasation time (τ). Conclusions. Extravasation of PAMAM dendrimers across the microvascular endothelium showed size and molecular weight dependence. Results suggest that in addition to size and molecular weight, other physicochemical properties of polymeric drug carriers such as molecular geometry and charge may influence their microvascular extravasation. Systematic studies of the influence of the physicochemical properties of polymeric drug carriers on their microvascular extravasation will aid in the design of novel macromolecular drug carriers with controlled extravasation profiles. [ABSTRACT FROM AUTHOR]

Poly(amidoamine) dendrimers (PAMAM) are polymeric macromolecules that can find their use as carriers of small ligand molecules such as cosmetics and drugs. 5- Fluorouracil is a potent oncological drug, whose usage is limited because of its relatively high toxicity.The surface and internal layer groups in PAMAM dendrimer belonging to the third (G3) generation create an open-type structure, which facilitate small ligand molecules to bind with them.The formation equilibrium of PAMAM G3 dendrimer complex with an oncologic drug such as 5 fluorouracil (FU) in water at room temperature was examined. Using the results of the drug solubility in dendrimer solutions, the maximal number of drug molecules in the dendrimer-drug complex was evaluated. Solubility results show that PAMAM G3 dendrimer can transfer tens 5 fluorouracil molecules in aqueous solution.This research work was funded from the Polish budget appropriations for science in the years 2013-2015, project number IP2012 022372.

The objective of this study was to investigate the difference in electrophoretic mobility between partially and fully poly(ethylene glycol)-conjugated poly(amidoamine) dendrimers (part-PEG-PAMAM and full-PEG-PAMAM, respectively) using a microchip capillary gel electrophoresis (MCGE). While MCGE allowed size-based separation of PEG-PAMAMs prepared with monomethoxy PEG-nitrophenyl carbonate, full-PEG-PAMAMs migrated slower than part-PEG-PAMAMs that were similar in size or larger. When the measured molecular weights obtained from MCGE analysis and the calculated molecular weights were plotted, each part-PEG-PAMAM and full-PEG-PAMAM showed correlation coefficients greater than 0.98. This study indicates that MCGE would be useful for characterizing PEG-PAMAMs with different PEGylation degrees. [ABSTRACT FROM AUTHOR]

• The novel engineered macrophages as a theranostic platform are developed. • Au DENPs can polarize macrophages into the M1-like phenotype. • The engineered macrophages can enhance CT imaging of the orthotopic osteosarcoma. • Au DENPs@Macs can be used as an effective theranostic platform for osteosarcoma. Immune cell therapy has recently emerged as a promising treatment modality for malignant tumors. Specifically, nanoparticle-mediated cell-immunotherapy has attracted considerable attention due to the combined contributions of the biological regulation of nanoparticles and the intrinsic nature of immune cells. Herein, engineered macrophages with dendrimer-entrapped gold nanoparticles (Au DENPs@Macs) were designed as a theranostic cell platform, for the first time, for CT imaging-guided cell immunotherapy and chemotherapy of osteosarcoma. In this study, Au DENPs were synthesized and used to activate macrophages into the anti-tumorigenic M1-like phenotype, characterized by the increased expression of CD86, the inducible type of nitric oxide synthase (iNOS), and tumor necrosis factor-α (TNF-α). After loading Au DENPs, the engineered macrophages showed cytostatic/pro-apoptotic effects against cancer cells and achieved CT imaging performance in vitro and in vivo. The combination of cell therapy and chemotherapy demonstrated a cooperative impact in enhancing cancer treatment. Our findings reveal that Au DENPs@Macs can be used as a theranostic platform for osteosarcoma, which may present a brand‐new strategy for immune cell-combined chemotherapy of other cancer types. [ABSTRACT FROM AUTHOR]