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1.
Int J Mol Sci ; 20(24)2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31835372

RESUMO

In a century when environmental pollution is a major issue, polymers issued from bio-based monomers have gained important interest, as they are expected to be environment-friendly, and biocompatible, with non-toxic degradation products. In parallel, hyperbranched polymers have emerged as an easily accessible alternative to dendrimers with numerous potential applications. Glycerol (Gly) is a natural, low-cost, trifunctional monomer, with a production expected to grow significantly, and thus an excellent candidate for the synthesis of hyperbranched polyesters for pharmaceutical and biomedical applications. In the present article, we review the synthesis, properties, and applications of glycerol polyesters of aliphatic dicarboxylic acids (from succinic to sebacic acids) as well as the copolymers of glycerol or hyperbranched polyglycerol with poly(lactic acid) and poly(ε-caprolactone). Emphasis was given to summarize the synthetic procedures (monomer molar ratio, used catalysts, temperatures, etc.,) and their effect on the molecular weight, solubility, and thermal and mechanical properties of the prepared hyperbranched polymers. Their applications in pharmaceutical technology as drug carries and in biomedical applications focusing on regenerative medicine are highlighted.


Assuntos
Materiais Biocompatíveis , Dendrímeros , Portadores de Fármacos , Glicerol , Poliésteres , Polímeros , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Dendrímeros/síntese química , Dendrímeros/química , Dendrímeros/uso terapêutico , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/uso terapêutico , Glicerol/síntese química , Glicerol/química , Glicerol/uso terapêutico , Humanos , Poliésteres/síntese química , Poliésteres/química , Poliésteres/uso terapêutico , Polímeros/síntese química , Polímeros/química , Polímeros/uso terapêutico , Medicina Regenerativa
2.
Chem Commun (Camb) ; 56(2): 301-304, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31808472

RESUMO

Bioimaging has revolutionized modern medicine, and nanotechnology can offer further specific and sensitive imaging. We report here an amphiphilic dendrimer able to self-assemble into supramolecular nanomicelles for effective tumor detection using SPECT radioimaging. This highlights the promising potential of supramolecular dendrimer platforms for biomedical imaging.


Assuntos
Dendrímeros/química , Nanoestruturas/química , Tensoativos/química , Adenocarcinoma/diagnóstico por imagem , Animais , Linhagem Celular Tumoral , Quelantes/síntese química , Quelantes/química , Dendrímeros/síntese química , Compostos Heterocíclicos com 1 Anel/síntese química , Compostos Heterocíclicos com 1 Anel/química , Humanos , Índio , Radioisótopos de Índio , Camundongos , Micelas , Neoplasias Pancreáticas/diagnóstico por imagem , Radioisótopos , Tensoativos/síntese química , Tomografia Computadorizada de Emissão de Fóton Único/métodos
3.
Colloids Surf B Biointerfaces ; 184: 110531, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31590053

RESUMO

Iron oxide-based magnetic resonance imaging (MRI) contrast agents have negative contrast limitations in cancer diagnosis. Gadolinium (Gd)-based contrast agents show toxicity. To overcome these limitations, Gd-doped ferrite (Gd:Fe3O4 (GdIO) nanoparticles (NPs) were synthesized as T1-T2 dual-modal contrast agents for MRI-traced drug delivery. A theranostics GdIO encapsulated in a Generation 4.5 PAMAM dendrimer (G4.5-GdIO) was developed by alkaline coprecipitation. The drug-loading efficiency of the NPs was ∼24%. In the presence of a low-frequency alternating magnetic field (LFAMF), a maximum cumulative doxorubicin (DOX) release of ∼77.47% was achieved in a mildly acidic (pH = 5.0) simulated endosomal microenvironment. Relaxometric measurements indicated superior r1 (5.19 mM-1s-1) and r2 (26.13 mM-1s-1) for G4.5-GdIO relative to commercially available Gd-DTPA. Thus, G4.5-GdIO is promising as an alternative noninvasive MRI-traced cancer drug delivery system.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Dendrímeros/química , Doxorrubicina/farmacologia , Nanopartículas/química , Poliaminas/química , Nanomedicina Teranóstica , Antibióticos Antineoplásicos/química , Cápsulas/síntese química , Cápsulas/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Meios de Contraste/síntese química , Meios de Contraste/química , Dendrímeros/síntese química , Doxorrubicina/química , Sistemas de Liberação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Compostos Férricos/química , Gadolínio/química , Células HeLa , Humanos , Imagem por Ressonância Magnética , Tamanho da Partícula , Poliaminas/síntese química , Propriedades de Superfície
4.
IET Nanobiotechnol ; 13(6): 560-564, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31432786

RESUMO

While cancer is the leading cause of human's deaths worldwide, finding an imaging agent which can detect cancer tumours is needed for cancer diagnosis. In the present study, PEG-citrate dendrimer-G2 was used as a nano-carrier of FITC dye and Iohexol to help passive targeting and uptake of both imaging agents in cancer cells/tumour in vitro and in vivo. Dendrimer was synthesisedand the product characterised using LC-MS, FT-IR, DLS, ELS, AFM, and 1HNMR. After FITC loading into dendrimer, MTT was performed to determine the cytotoxicity of formulation on HEK-293 and MCF-7 cells. In vitro imaging using dendrimer-FITC was done via fluorescent microscope thereafter. Moreover, CT imaging using Iohexol was employed to show the targeting nature and ability of the complex to use as imaging agent in vivo. Data yielded in this study corroborate the notion that the promised dendrimer was synthesised properly and had no toxicity along with FITC on normal cell. Furthermore, CT and fluorescent images showed the targeting nature and imaging ability of Iohexol/FITC loaded dendrimer in vitro and in vivo. Overall, results showed promising characteristics of the novel complexes using dendrimer-G2 both in vitro and in vivo.


Assuntos
Ácido Cítrico/química , Dendrímeros/química , Diagnóstico por Imagem/métodos , Corantes Fluorescentes/química , Polietilenoglicóis/química , Citratos/síntese química , Citratos/química , Dendrímeros/síntese química , Portadores de Fármacos , Fluoresceína-5-Isotiocianato/química , Corantes Fluorescentes/síntese química , Células HEK293 , Humanos , Células MCF-7 , Coloração e Rotulagem/métodos
5.
Proc Natl Acad Sci U S A ; 116(31): 15378-15385, 2019 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-31308223

RESUMO

Reconstructing the functions of living cells using nonnatural components is one of the great challenges of natural sciences. Compartmentalization, encapsulation, and surface decoration of globular assemblies, known as vesicles, represent key early steps in the reconstitution of synthetic cells. Here we report that vesicles self-assembled from amphiphilic Janus dendrimers, called dendrimersomes, encapsulate high concentrations of hydrophobic components and do so more efficiently than commercially available stealth liposomes assembled from phospholipid components. Multilayer onion-like dendrimersomes demonstrate a particularly high capacity for loading low-molecular weight compounds and even folded proteins. Coassembly of amphiphilic Janus dendrimers with metal-chelating ligands conjugated to amphiphilic Janus dendrimers generates dendrimersomes that selectively display folded proteins on their periphery in an oriented manner. A modular strategy for tethering nucleic acids to the surface of dendrimersomes is also demonstrated. These findings augment the functional capabilities of dendrimersomes to serve as versatile biological membrane mimics.


Assuntos
Dendrímeros/química , Interações Hidrofóbicas e Hidrofílicas , Ácidos Nucleicos/química , Proteínas/química , Dendrímeros/síntese química , Proteínas de Fluorescência Verde/química , Ligantes , Lipossomos/química , Ácido Nitrilotriacético/química , Propriedades de Superfície
6.
Curr Med Chem ; 26(35): 6349-6398, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31203794

RESUMO

Carbohydrates are one of the most powerful and versatile classes of biomolecules that nature uses to regulate organisms' biochemistry, modulating plenty of signaling events within cells, triggering a plethora of physiological and pathological cellular behaviors. In this framework, glycan carrier systems or carbohydrate-decorated materials constitute interesting and relevant tools for medicinal chemistry applications. In the last few decades, efforts have been focused, among others, on the development of multivalent glycoconjugates, biosensors, glycoarrays, carbohydrate-decorated biomaterials for regenerative medicine, and glyconanoparticles. This review aims to provide the reader with a general overview of the different carbohydrate carrier systems that have been developed as tools in different medicinal chemistry approaches relying on carbohydrate-protein interactions. Given the extent of this topic, the present review will focus on selected examples that highlight the advancements and potentialities offered by this specific area of research, rather than being an exhaustive literature survey of any specific glyco-functionalized system.


Assuntos
Química Farmacêutica/métodos , Polissacarídeos/uso terapêutico , Animais , Técnicas Biossensoriais/métodos , Dendrímeros/síntese química , Dendrímeros/metabolismo , Dendrímeros/uso terapêutico , Portadores de Fármacos/síntese química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/uso terapêutico , Humanos , Nanopartículas/química , Nanopartículas/metabolismo , Nanopartículas/uso terapêutico , Polissacarídeos/síntese química , Polissacarídeos/metabolismo , Ligação Proteica , Proteínas/metabolismo
7.
Luminescence ; 34(6): 615-622, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31106961

RESUMO

A new near-infrared fluorescence sensor PDI-PD for Ag+ ions was successfully prepared and its structure characterized by 1 H nuclear magnetic resonance (NMR), 13 C NMR and high-resolution mass spectrometry; matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (HRMS MALDI-TOF). The probe exhibited rapid, sensitive, and selective two-channel fluorescence responses towards Ag+ ions and protons. The probe has a marked high binding affinity and high sensitivity for Ag+ , with a detection limit of 1.4 × 10-6  M. An approximately five-fold enhanced core emission at 784 nm was attributed to fluorescence resonance energy transfer (FRET). The enhanced core emission of the probe with Ag+ ions based on photo-induced electron transfer and FRET is discussed. In addition, the probe presented a visible colour change. All experimental results demonstrated that PDI-PD is an efficient tool for the selective, sensitive and rapid detection of Ag+ ions and protons using two-channel fluorescence responses.


Assuntos
Dendrímeros/química , Prata/química , Espectrometria de Fluorescência/métodos , Dendrímeros/síntese química , Fluorescência , Transferência Ressonante de Energia de Fluorescência , Limite de Detecção
8.
PLoS One ; 14(5): e0217369, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31125361

RESUMO

Multivalent proteins or protein dendrimers are useful for clinical and biotechnological applications. However, assembly of chemically defined protein dendrimers is a challenging endeavor. In the past, majority of protein dendrimers have been developed on branched lysine scaffolds and are usually limited to a valency of two to four. The naturally occurring cyclodextrin (CD) scaffold composed of 6-8 glucose units offers the possibility of expanding the valency. Here we have adapted a chemoenzymatic-click strategy for displaying heptavalent peptides and large proteins on the ß-cyclodextrin (ß-CD) scaffold. We demonstrate that recombinant proteins (engineered with a LPXTG pentapeptide motif at the carboxy terminus), labeled with an alkyne moiety by sortase-mediated ligation, can be easily clicked on to the azide-derivatized ß-cyclodextrin through the Huisgen cycloaddition reaction yielding a well-defined heptavalent display of proteins.


Assuntos
Aminoaciltransferases/metabolismo , Proteínas de Bactérias/metabolismo , Química Click/métodos , Reação de Cicloadição/métodos , Ciclodextrinas/química , Cisteína Endopeptidases/metabolismo , Peptídeos/química , Sequência de Aminoácidos , Aminoaciltransferases/genética , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Cisteína Endopeptidases/genética , Dendrímeros/síntese química , Dendrímeros/química , Proteínas de Fímbrias/química , Proteínas de Fímbrias/genética , Proteínas de Fímbrias/metabolismo , Modelos Moleculares , Biossíntese Peptídica , Peptídeos/síntese química , Engenharia de Proteínas/métodos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
9.
Biopolymers ; 110(7): e23272, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30897210

RESUMO

Oxaliplatin (OXA) was coupled to PEGylated polyamidoamine dendrimers of fourth generation (G4-PEG@OXA) in the comparison to PEGylated ones of odd generation (G3.5-PEG@OXA). Proton nuclear magnetic resonance and Fourier-transform infrared spectroscopy were used to confirm the successful incorporation of OXA as well as the synthesis of carrier systems. Both two types of carrier systems exhibited in sphere nanoparticle shape with size of less than 100 nm that was in the range being able to cause toxicity on cancer cells. The average drug loading efficiency (DLE) of G4-PEG@OXA was obtained at 84.63% that was higher than DLE of G3.5-PEG of 75.69%. The release kinetic of G4-PEG@OXA and G3.5-PEG@OXA did not show any burst release phenomenon while free OXA was released over 40% at the first hour. The sustainable release of OXA was achieved when it was encapsulated in these carriers, but the G4 generation liberated OXA (3.4%-6.4%) slower than G3.5 one (11.9%-22.8%). The in vitro cytotoxicities of G4-PEG@OXA were evaluated in HeLa cell lines using resazurin assay and live/dead staining test. Although the free OXA showed a rather moderate killing ability, the G4-PEG@OXA still displayed the low viability of HeLa that was better to the result of G3.5-PEG@OXA due to released OXA amount. The benefit of this system was to overcome the burst release phenomenon to minimize OXA toxicity without compromising its efficiency.


Assuntos
Antineoplásicos/farmacologia , Preparações de Ação Retardada/síntese química , Dendrímeros/síntese química , Portadores de Fármacos/síntese química , Nanopartículas/química , Oxaliplatina/farmacologia , Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Células HeLa , Humanos , Cinética , Nanopartículas/ultraestrutura , Oxaliplatina/química , Tamanho da Partícula , Poliaminas/química , Polietilenoglicóis/química
10.
Biomolecules ; 9(3)2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30841638

RESUMO

BACKGROUND: Exposure to ozone level and ultraviolet (UV) radiation is one of the major concerns in the context of public health. Numerous studies confirmed that abundant free radicals initiate undesired processes, e.g. carcinogenesis, cells degeneration, etc. Therefore, the design of redox-active molecules with novel structures, containing radical quenchers molecules with novel structures, and understanding their chemistry and biology, might be one of the prospective solutions. Methods: We designed a group of peptide dendrimers carrying multiple copies of p-aminobenzoic acid (PABA) and evaluated their molecular antioxidant properties in 1,1'-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) tests. Cytotoxicity against human melanoma and fibroblast cells as well as against primary cerebral granule cells (CGC) alone and challenged by neurotoxic sodium glutamate and production of reactive oxygen species (ROS) in presence of dendrimers were measured. Results: PABA-terminated dendrimers express enhanced radical and radical cation scavenging properties in relation to PABA alone. In cellular tests, the dendrimers at 100 M fully suppress and between 20⁻100 M reduce proliferation of the human melanoma cell line. In concentration 20 M dendrimers generate small amount of the reactive oxygen species (<25%) but even in their presence human fibroblast and mouse cerebellar granule cells remain intact Moreover, dendrimers at 0.2⁻20 µM concentration (except one) increased the percentage of viable fibroblasts and CGC cells treated with 100 M glutamate. Conclusions: Designed PABA-functionalized peptide dendrimers might be a potential source of new antioxidants with cationic and neutral radicals scavenging potency and/or new compounds with marked selectivity against human melanoma cell or glutamate-stressed CGC neurons. The scavenging level of dendrimers depends strongly on the chemical structure of dendrimer and the presence of other groups that may be prompted into radical form. The present studies found different biological properties for dendrimers constructed from the same chemical fragments but the differing structure of the dendrimer tree provides once again evidence that the structure of dendrimer can have a significant impact on drug⁻target interactions.


Assuntos
Ácido 4-Aminobenzoico/farmacologia , Antioxidantes/farmacologia , Benzotiazóis/antagonistas & inibidores , Compostos de Bifenilo/antagonistas & inibidores , Dendrímeros/farmacologia , Fibroblastos/efeitos dos fármacos , Peptídeos/farmacologia , Picratos/antagonistas & inibidores , Ácidos Sulfônicos/antagonistas & inibidores , Ácido 4-Aminobenzoico/química , Animais , Antioxidantes/síntese química , Antioxidantes/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dendrímeros/síntese química , Dendrímeros/química , Relação Dose-Resposta a Droga , Humanos , Camundongos , Estrutura Molecular , Peptídeos/síntese química , Peptídeos/química , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade
11.
Food Chem ; 285: 450-457, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30797369

RESUMO

We synthesized polyamidoamine (PAMAM) dendrimers and citrate-capped gold nanoparticles (AuNPs), and explored the applicability of the PAMAM/AuNP assay in determining total free fatty acid (FFA) contents in edible oils based on a competitive colorimetry, in which the PAMAM-triggered AuNP aggregation was suppressed by FFAs. The generation and concentration of PAMAMs, the chain lengths of FFAs as well as the concentration and pH of the background electrolytes of the assay were optimized. The average acid values of the sunflower seed, corn and extra virgin olive oils determined by PAMAM/AuNP assay were 1.31 ±â€¯0.07, 0.33 ±â€¯0.02 and 1.49 ±â€¯0.07, respectively, which were not significantly different from the corresponding 1.27 ±â€¯0.08, 0.32 ±â€¯0.01 and 1.61 ±â€¯0.06 by the standard nonaqueous titration. Our results suggest that the method is promising in detecting FFAs in edible oils, and implementation of the method expands the technological scope for FFA analysis.


Assuntos
Colorimetria/métodos , Ácidos Graxos não Esterificados/análise , Análise de Alimentos/métodos , Nanopartículas Metálicas/química , Óleos Vegetais/análise , Colorimetria/instrumentação , Dendrímeros/síntese química , Dendrímeros/química , Ouro/química , Concentração de Íons de Hidrogênio , Azeite de Oliva/análise , Azeite de Oliva/química , Óleos Vegetais/química , Poliaminas/química
12.
Bioorg Chem ; 86: 452-458, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30772646

RESUMO

The increasing use of dendrimers shows promise for the treatment of inflammatory diseases, Chagas disease and other conditions such as cancer. In this study, the activity of 1st and 2nd generation dendrimers over T. cruzi in the epimastigote stage was tested. Dendrimers were derived from α-ethynylestradiol (EE) modified with PAMAM-type dendrons through a triazole ring. The activity of each compound was evaluated in five doses (from 1.3 to 20 µmol/mL) by flow cytometry, including benznidazole (Bz) as positive control. The findings show that an equivalent concentration of 14.8 µmol/mL of 2nd generation (G) dendrimer is 8 times more effective than Bz at 24 h, and it maintains its superiority at 48 h with an IC50 = 1.25 ±â€¯0.19 µmol/mL. A TUNEL assay showed that dendrimers induce cell death in T. cruzi epimastigotes mostly via apoptosis, unlike Bz, which induces death via necrosis in more than 50% of cells.


Assuntos
Dendrímeros/farmacologia , Poliaminas/farmacologia , Esteroides/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Química Click , Dendrímeros/síntese química , Dendrímeros/química , Relação Dose-Resposta a Droga , Humanos , Linfócitos/efeitos dos fármacos , Estrutura Molecular , Testes de Sensibilidade Parasitária , Poliaminas/química , Esteroides/síntese química , Esteroides/química , Relação Estrutura-Atividade , Trypanosoma cruzi/crescimento & desenvolvimento
13.
Theranostics ; 9(2): 337-354, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30809278

RESUMO

High-efficiency treatment for tumor is not easy to achieve owing to the existence of metastasis, which remains the arch-criminal of most tumor deaths. Conventional chemotherapy exhibits insufficient inhibitory efficiency on tumor metastasis and more powerful strategies to conquer metastatic tumors are urgently needed. In this study, a rational chemoimmunotherapy strategy was adopted to treat highly aggressive melanoma based on a newly developed multifunctional nanoplatform. Firstly, immunoadjuvant cytosine-phosphate-guanine oligonucleotides (CpG ODNs) were used to boost the doxorubicin (DOX)-elicited immune responses, which synergistically suppressed tumor growth and metastasis. And the anti-metastatic low molecular weight heparin (LMWH) was also integrated, thus multiple anti-metastatic effects to against tumor metastasis were achieved. Methods: G4 PAMAM was serving as the main support to conjugate DOX by pH-sensitive hydrazone bond (PPD) and the synthesized conjugates were confirmed by 1H-NMR spectra, IR spectra and HRMS. Immunoadjuvant CpG ODNs were loaded by electrostatic adsorption to formulate PPD/CpG. After the coating of anti-metastatic LMWH, the designed LMWH/PPD/CpG was fabricated and characterized. The platelets-related and platelets-unrelated anti-metastatic mechanisms were investigated on B16F10 the immune activation effects, anti-tumor and anti-metastatic efficacy of LMWH/PPD/CpG were evaluated on a B16F10 melanoma xenograft model. Results: DOX elicited tumor-specific immune responses by ICD, and the immunological effects could be further promoted by CpG ODNs, exhibiting enhanced maturation of dendritic cells (DCs) and increased level of cytolytic T lymphocytes (CTLs) in vivo. Owing to the coating of LMWH, the platelets-induced epithelial-mesenchymal-like transition of tumor cells was hindered and the actin cytoskeletal arrangement of tumor cells was affected, thus the migration ability of tumor cells was further inhibited. This multifunctional nanoplatform showed enhanced treatment efficiency on melanoma primary tumor and pulmonary metastasis. Conclusion: The immune activation and multiple anti-metastatic effects of LMWH/PPD/CpG establish a novel therapeutic strategy for melanoma. This anti-metastatic nanoplatform could be broadly applied for the co-delivery of other nucleic acids and chemotherapeutic drugs to treat highly aggressive tumors.


Assuntos
Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Heparina de Baixo Peso Molecular/administração & dosagem , Fatores Imunológicos/administração & dosagem , Melanoma/tratamento farmacológico , Nanoestruturas/administração & dosagem , Oligodesoxirribonucleotídeos/administração & dosagem , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Técnicas Citológicas , Dendrímeros/administração & dosagem , Dendrímeros/síntese química , Modelos Animais de Doenças , Humanos , Camundongos , Modelos Teóricos , Transplante de Neoplasias , Transplante Heterólogo , Resultado do Tratamento
14.
Org Biomol Chem ; 17(11): 2906-2912, 2019 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-30672956

RESUMO

Herein, we report the design and synthesis of two novel bifunctional dendrons bearing multiple amine termini at the periphery and an azide at the focal point. Copper-catalyzed alkyne-azide cycloaddition enabled modular dendritic scaffold assembly resulting in a first generation dendron carrying six amines and a second generation dendron carrying eighteen amines. Peripheral amines were labeled with multiple copies of a metal isotope, whereas the azide functionality at the focal point was employed in conjugation to a single anti-human CD4 antibody. We demonstrated that the highly monomeric first generation dendron-antibody conjugate selectively detected CD4+ T cells in the PMBC culture.


Assuntos
Aminas/química , Anticorpos/química , Azidas/química , Dendrímeros/química , Aminas/imunologia , Anticorpos/imunologia , Reações Antígeno-Anticorpo , Azidas/imunologia , Antígenos CD4/química , Antígenos CD4/imunologia , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Catálise , Células Cultivadas , Cobre/química , Dendrímeros/síntese química , Humanos , Estrutura Molecular
15.
Colloids Surf B Biointerfaces ; 176: 404-411, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30660964

RESUMO

Letrozole as a target loaded drug on siliceous magnetized Fe3O4 nanoparticles grafted with high-branched dendrimers. Grafted polymer coating contained N-vinyl caprolactam as a stimulus-responsive polymer which functionalized with five generations of dendrimers containing oxime functional group. The precursors underwent PEGylating polymerization to form PEGylated dendrimer coating on the particle surface as the final carrier. The final product has the average size of ˜79 nm. The final product characterized by FT-IR, TGA, VSM, SEM-EDAX to investigate carrier features further. Some characteristic parameters in adsorption process like pH, time, the temperature investigated for letrozole using the final carrier. The physical and chemical properties of the final polymerized generations were also studied. Letrozole releasing process examined in the simulated intestinal fluid (pH = 7.4) revealed 95% of letrozole released during 25 h which also considered by Korsmeyer-Peppas equation to verify Fickian diffusion mechanism.


Assuntos
Dendrímeros/síntese química , Sistemas de Liberação de Medicamentos , Letrozol/administração & dosagem , Magnetismo , Polietilenoglicóis/química , Polietilenoglicóis/síntese química , Polímeros/química , Temperatura , Adsorção , Dendrímeros/química , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Cinética , Letrozol/farmacologia , Magnetometria , Modelos Teóricos , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria , Fatores de Tempo , Vibração
16.
J Inorg Biochem ; 193: 31-41, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30669064

RESUMO

Supramolecular Janus compounds have recently attracted increasing attention owing to their dynamic reversible properties, distinct topological structures, and remarkable physicochemical characteristics, e.g., amphiphilicity, heterofunctionality, and high-density of terminal groups. Herein, a new redox-responsive supramolecular Janus device was designed and synthesized involving ß-cyclodextrin and 2-fold ferrocene host-guest interactions. The complex formation was analyzed via one-dimensional 1H NMR and two-dimensional Nuclear Overhauser Enhancement Spectroscopy. FeCl3 and ascorbic acid were used as oxidation and reduction triggers, respectively, to modulate the self-assembly behavior in water through complexation/dissociation of ß-cyclodextrin inclusion compounds resulting from redox-conversion of the ferrocenyl guest moieties. The redox-responsiveness of the obtained supramolecular micelles was studied via scanning electron microscopy and dynamic light scattering. Substrate-loading ability of the supramolecular micelles was confirmed with Rhodamine B, and the oxidation of ferrocenyl groups led to the release of the loaded cargos. The present work illustrates a valuable design example of supramolecular Janus systems using the host-guest complexation between ß-cyclodextrin and ferrocenyl structures. The present supramolecular micelle may be used as a promising molecular vehicle for application in the field of stimuli-responsive drug delivery.


Assuntos
Dendrímeros/química , Portadores de Fármacos/química , Compostos Ferrosos/química , Rodaminas/química , beta-Ciclodextrinas/química , Ácido Ascórbico/química , Cloretos/química , Dendrímeros/síntese química , Portadores de Fármacos/síntese química , Liberação Controlada de Fármacos , Compostos Férricos/química , Compostos Ferrosos/síntese química , Corantes Fluorescentes/química , Micelas , Oxirredução
17.
Carbohydr Polym ; 204: 104-110, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30366521

RESUMO

Glucan dendrimers (GDs) were synthesized by using a branching enzyme. Spherical GDs of different molecular weights were obtained and had a narrow particle size distribution. Small-angle X-ray scattering (SAXS) measurements showed that the radius of gyration of the GDs was 4.2-14.6 nm in aqueous solution. The SAXS profiles of GDs with small molecular weights exhibited scattering behavior similar to that described by the hyperbranched polymer model, and tended to resemble that of a sphere as the molecular weight increased.


Assuntos
Enzima Ramificadora de 1,4-alfa-Glucana/química , Dendrímeros/química , Glucanos/química , Amido/química , Bactérias/enzimologia , Dendrímeros/síntese química , Glucanos/síntese química , Peso Molecular , Tamanho da Partícula , Espalhamento a Baixo Ângulo , Difração de Raios X
18.
Macromol Rapid Commun ; 40(6): e1800571, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30480853

RESUMO

Multicomponent miktoarm stars (MMSs) comprising at least three kinds of chemically different arm segments are extremely important due to their great potential as multiphase materials to elucidate composition/topology-dependent properties and applications. At present, a "core first" route gives ABC stars, "coupling onto" and combinatorial methods afford ABC and ABCD stars, and modular and iterative approaches enable facile synthesis of MMSs with five or more components. Meanwhile, the introduction of stimuli-labile linkages and couplable groups into star polymers further enriches the family of smart materials. Upon external stimuli, linking reaction, or postpolymerization modification, miktoarm stars are potentially converted into other architectural polymers such as linear, tadpole-like, graft, and dendrimer-like polymers via cleavage and rearrangement in the chain structure. This feature article aims to systematically summarize the synthetic methods and versatile topological transitions of ABC, ABCD, and ABCDE stars. The advantages and limitations of each approach are highlighted, and the future considerations on developments and challenges are discussed.


Assuntos
Polímeros/síntese química , Dendrímeros/síntese química , Dendrímeros/química , Estrutura Molecular , Polimerização , Polímeros/química
19.
Macromol Rapid Commun ; 40(1): e1800711, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30474179

RESUMO

The design of dendrimers with various chromophores has attracted significant attention in light of the dual effect of the luminescence of the chromophores and the morphology of the synthesized dendrimers. Recent developments in this field stem from their wide potential applications, including organic light-emitting diodes, photonic switches and upconversion lasers, as well as sensors and electronic devices. The focus of this comprehensive review is on the design and properties of various classes of light-harvesting dendrimeric materials.


Assuntos
Dendrímeros/química , Luz , Dendrímeros/síntese química , Luminescência
20.
Langmuir ; 35(5): 1613-1620, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30558421

RESUMO

As one of the most promising therapeutic methods, gene therapy has been playing a more and more important role in treating disease due to its ultra-high therapy efficiency. Even if nonviral gene vectors represented by polycation, liposomal, dendrimers, and zwitterionic materials have made great progress in gene complexation, low immunogenicity, and biocompatibility, intracellular gene release with low toxicity is effectively still a bottleneck restricting the clinical application of gene therapy. We designed and synthesized a reactive oxygen species (ROS)-responsive dendrimer poly(amido amine)- N-(4-boronobenzyl)- N, N-diethyl-2-(propionyloxy)ethan-1-aminium (PAMAM-(B-DEAEP)16) as a gene vector whose potential can vary from positive to negative under the elevated ROS (H2O2) in cancerous cells. Dynamic light scattering results showed that the zeta potential of PAMAM-(B-DEAEP)16 decreased from +12.3 to -5 mV under 80 mM H2O2 in PBS buffer. The 1H NMR results demonstrated that the intermediate status of PAMAM-(B-DEAEP)16 was zwitterionic in ∼6 h because it consisted of the positive quaternary ammonium and negative carboxylic acid simultaneously before the ester bond was completely hydrolyzed. Gel retardation assay showed that PAMAM-(B-DEAEP)16 can condense DNA at above N/P = 1; then, PAMAM-(B-DEAEP)16 transfers to zwitterionic, which begins to continuously release DNA with the decrease in the positive charges and increase in the negative charges, and finally to negatively charged poly(amido amine)-propionic acid (PAMAM-PAc16) in the 80 mM H2O2. Fluorescence-labeled Cy-5 DNA indicated that PAMAM-(B-DEAEP)16 can enter into the cell completely in ∼4 h. The results showed that this compound we designed exhibited higher gene transfection efficiency and lower cytotoxicity than commercial PEI. This is the first time that the positively charged dendrimer was transferred to zwitterionic dendrimer under the stimuli of H2O2 and was successfully applied to gene delivery. Unlike all of the previous reports, we did not seek a compromise between the high gene transfection and low toxicity but find a new avenue to make the gene carrier not only have higher gene transfection efficiency but also exhibit lower toxicity by introducing stimuli-sensitive groups into the positively charged dendrimer to make it capable of adjusting the charge property according to the microenvironment. This study not only provides a good method to design materials for gene delivery but also opens a new perspective to understand the process of gene delivery.


Assuntos
DNA/metabolismo , Dendrímeros/metabolismo , Poliaminas/química , Dendrímeros/síntese química , Dendrímeros/toxicidade , Técnicas de Transferência de Genes , Células HeLa , Humanos , Peróxido de Hidrogênio/metabolismo , Poliaminas/síntese química
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