Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 9 de 9
Filtrar
1.
Soft Matter ; 16(30): 7033-7039, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32667008

RESUMO

We herein report the construction of peroxidase (POD)-mimicking catalysts based on the strategy of peptide assembly and molecular imprinting. Upon co-assembly of Fmoc-FFH and Hemin, we firstly fabricated CA-H/Hemin which displayed POD-like catalytic activity and showed a 21-fold rate acceleration in the oxidation of 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) compared to the uncatalyzed reaction. Then, upon combining CA-H/Hemin with the ABTS-imprinted polymer, the obtained imprinted catalyst (MIP-H/Hemin) showed 52-fold acceleration due to the enhanced re-binding toward ABTS. Moreover, by introducing cationic monomers, a 137-fold rate enhancement was further achieved for the positively charged imprinted catalyst (MIP+-H/Hemin), from the synergistic effect of molecular imprinting and electrostatic attraction. Remarkably, by comparing the catalytic activity of these POD mimics towards ABTS and 3,3',5,5'-tetramethylbenzidine (TMB), we also highlighted the substrate specificity of MIP-H/Hemin and MIP+-H/Hemin toward ABTS. This study provides a promising approach to improve the catalytic activity and specificity of peptide-based enzyme mimics.


Assuntos
Impressão Molecular , Catálise , Hemina , Peptídeos , Polímeros
2.
J Nanosci Nanotechnol ; 12(6): 4467-71, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22905486

RESUMO

The main purpose of this study was to evaluate the targeting effect of cyclic arginine-glycine-aspartic peptide (cRGD)-modified monomethoxy (polyethylene glycol)-poly (D, L-lactide-co-glycolide)-poly (L-lysine) nanoparticles (mPEG-PLGA-PLL-cRGD NPs) for gastric cancer SGC-7901 cells. We prepared the 5-Fulorouracil (5Fu)-loaded mPEG-PLGA-PLL-cRGD (5Fu/mPEG-PLGA-PLL-cRGD) NPs that had an average particle size of 180 nm and a zeta potential 2.77 mV. The results of cytotoxicity demonstrated the mPEG-PLGA-PLL-cRGD NPs showed the ignorable cytotoxicity and the 5Fu/mPEG-PLGA-PLL-cRGD NPs could significantly enhance the cytotoxicity of 5Fu. In vitro drug release experiments showed that the release of drug was effectively prolonged and sustained. The results of confocal laser scanning microscope (CLSM) and flow cytometer analysis demonstrated that the fluorescence intensity of the SGC-7901 gastric cancer cells treated with Rb/mPEG-PLGA-PLL-cRGD NPs was significantly higher than that treated with Rb, this suggested that Rb/mPEG-PLGA-PLL-cRGD NPs could effectively be internalized by SGC-7901 gastric cancer cells. In summary, the above experimental results illustrate that mPEG-PLGA-PLL-cRGD NPs have great potential to be used as an effective delivery carriers.


Assuntos
Fluoruracila/administração & dosagem , Terapia de Alvo Molecular/métodos , Nanocápsulas/química , Poliésteres/química , Polietilenoglicóis/química , Polilisina/análogos & derivados , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Linhagem Celular Tumoral , Difusão , Fluoruracila/química , Humanos , Teste de Materiais , Nanocápsulas/administração & dosagem , Peptídeos Cíclicos , Polilisina/química , Resultado do Tratamento
3.
Int J Mol Sci ; 13(1): 516-533, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22312268

RESUMO

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


Assuntos
Materiais Biocompatíveis/química , Nanopartículas/metabolismo , Polietilenoglicóis/química , Poliglactina 910/química , RNA Interferente Pequeno/metabolismo , Materiais Biocompatíveis/metabolismo , Materiais Biocompatíveis/toxicidade , Carbocianinas/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Humanos , Lipídeos/química , Microscopia de Fluorescência , Nanopartículas/química , Nanopartículas/toxicidade , Tamanho da Partícula , Poliésteres , Polietilenoglicóis/metabolismo , Polietilenoglicóis/toxicidade , Poliglactina 910/metabolismo , Poliglactina 910/toxicidade , Interferência de RNA , RNA Interferente Pequeno/genética , Transfecção
4.
ACS Nano ; 13(11): 12438-12444, 2019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31560190

RESUMO

Enantiodifferentiation is crucial in organic chemistry, pharmacochemistry, material chemistry, and life science. However, it remains tremendously challenging to achieve a broad enantioselectivity to different types of chiral substrates via a single-material design. Here, we report a coassembled organogel strategy with chirality transfer to make an enantioselective generality possible. This coassembly contains two components: a chiral rigid molecular linker and an achiral block copolymer. Different from routine helically packed chiral self-assemblies, chirality transfer from the linker to the copolymer directed the coassembly to form a phase-segregated twisted nanofiber, in cooperation with H-bonding and microphase segregation. An organogel was accordingly formed by the further cross-linking in ethanol, where the rigid chiral linker served as the scaffold. On this basis, the system becomes highly sensitive, enabling a naked-eye sensing toward the single enantiomer of a diverse series of chiral species (including axial, point, planar, and polymeric chirality) via gel-to-micelle transformation, due to the asymmetric interaction hampering the chirality transfer in the coassembly and destroying the hierarchical structure. Such a strategy, based on a significant amplification of the stereoselective interactions, facilitates a simple and straightforward way to distinguish a broad optical activity independent of devices.


Assuntos
Géis , Nanofibras , Polímeros , Géis/química , Géis/metabolismo , Humanos , Ligação de Hidrogênio , Teste de Materiais , Estrutura Molecular , Nanofibras/química , Nanofibras/ultraestrutura , Polímeros/química , Polímeros/metabolismo , Estereoisomerismo
5.
Nanotoxicology ; 9(2): 190-200, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24787691

RESUMO

A facile room-temperature method was used to prepare phosphatidylserine (PS)-poly(ethylene glycol) (PEG)/calcium phosphate (CaP) nanospheres (PS-poly(ethylene glycol) methyl ether/CaP nanospheres). Transmission electron microscopy (TEM) results confirmed that the PS-PEG/CaP porous nanospheres were spherical with a diameter of 8-12 nm. X-ray and thermo-gravimetric analysis (TGA) results also confirmed that the PS-PEG micelle was packed in the CaP shell. PS-PEG/CaP nanospheres exhibited little effect on the hemolysis, coagulation characteristics of blood and inflammatory response, demonstrating a negligible cytotoxicity response in LO2 liver cells. Experiments performed in zebrafish demonstrated that the PS-PEG/CaP nanospheres had a long circulatory residence time and did not induce apoptosis in zebrafish. Taken together, these results suggest that the PS-PEG/CaP nanospheres have great potential to be used as a drug carrier.


Assuntos
Fosfatos de Cálcio/efeitos adversos , Hepatócitos/fisiologia , Nanocápsulas/efeitos adversos , Nanocápsulas/química , Nanosferas/efeitos adversos , Peixe-Zebra/fisiologia , Animais , Materiais Biocompatíveis/efeitos adversos , Materiais Biocompatíveis/síntese química , Fosfatos de Cálcio/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Humanos , Teste de Materiais , Taxa de Depuração Metabólica/fisiologia , Nanosferas/química , Tamanho da Partícula , Fosfatidilserinas/efeitos adversos , Fosfatidilserinas/química , Polietilenoglicóis/química , Polietilenoglicóis/toxicidade , Coelhos , Taxa de Sobrevida , Distribuição Tecidual
6.
J Biomater Sci Polym Ed ; 25(9): 943-64, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24811211

RESUMO

Biomaterial poly(lactic-co-glycolic acid) (PLGA), a FDA-approved material for clinical application, showed broad prospects in the past, but gradually can no longer meet present clinical developments and requirements, which we synthesized monomethoxy(polyethylene glycol)-poly(D,L-lactic-co-glycolic acid)-poly(L-lysine) (mPEG-PLGA-PLL) (PEAL) and have had some relevant reports. But studies on biocompatibility and the impacts of LA and GA ratio (LA/GA=60/40, 70/30, and 80/20) in main material have not yet been reported. Hemolysis experiment indicates that the hemolysis rate of PEAL extraction medium is less than 5%. Whole blood clotting time (CT), plasma recalcification time, activated partial thromboplastin time, prothrombin time evaluations, and dynamic CT assay show that the anticoagulant time of PEAL copolymer for blood is longer than that under negative and positive control. Protein adsorption assay indicates that PEAL films adsorb less protein than PLGA films (p<0.01); but comparing with expanded polytetrafluoroethylene, the aforementioned difference is not significant (p>0.05). Complement activation test shows that PEAL surface does not induce complement activation. CCK8 measurement shows that the relative growth rates of Huh7, L02, and L929 cells co-incubated with PEAL nanoparticles (NPs) are more than 90%. PEAL NPs co-incubated with 5% foetal bovine serum or 2% bovine serum albumin, through dynamic light scattering assay, remain stable. Different concentrations of PEAL NPs co-incubated with zebrafish embryos at 6-72 h post fertilization show that comparing with negative control, 10, 100, or 500 µM of NPs for embryos development has no significant effects (p>0.05), only 1000 or 2000 µM of NPs has some effects (p<0.05). It is concluded that the PEAL copolymer, with excellent biocompatibility, proves to be a high-safety dose as drug carrier and implant candidate in vivo.


Assuntos
Glicolatos/química , Ácido Láctico/química , Teste de Materiais , Poliésteres/química , Poliésteres/toxicidade , Polietilenoglicóis/química , Polietilenoglicóis/toxicidade , Adsorção , Animais , Testes de Coagulação Sanguínea , Linhagem Celular , Proteínas do Sistema Complemento/química , Proteínas do Sistema Complemento/metabolismo , Relação Dose-Resposta a Droga , Feminino , Hemólise/efeitos dos fármacos , Humanos , Masculino , Camundongos , Nanopartículas/química , Nanopartículas/toxicidade , Relação Estrutura-Atividade , Peixe-Zebra/embriologia
7.
Biomaterials ; 34(16): 4068-4077, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23480957

RESUMO

Construction on the nanoparticles with lower toxicity and specific tumor targeting properties is challenging and requires careful design of composition, size, physicochemical properties tailored for the nanoparticles. Here the epidermal growth factor (EGF) modified methoxy polyethylene glycol-polylactic-co-glycolic acid-polylysine (mPEG-PLGA-PLL) encapsulated cisplatin (CDDP) nanoparticles (CDDP-NPs-EGF) was prepared to for solving the toxicity of CDDP and improving therapeutic efficiency. The remarkable features of CDDP-NPs-EGF are increasing cytotoxicity that attribute to effective cell cycle arrest and high cell apoptosis in vitro. In vivo, the CDDP-NPs-EGF change drug distribution, decrease the nephrotoxicity of CDDP and improve significantly therapeutic efficiency without inducing obvious system toxicity, verifying its key role of the CDDP-NPs-EGF in lowering drug toxicity and enhancing the antitumor efficiency for SKOV3 cancer in mice.


Assuntos
Cisplatino/uso terapêutico , Fator de Crescimento Epidérmico/farmacologia , Nanopartículas/toxicidade , Neoplasias Ovarianas/tratamento farmacológico , Poliésteres/química , Polietilenoglicóis/química , Polilisina/química , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Feminino , Citometria de Fluxo , Humanos , Camundongos , Microscopia Confocal , Nanopartículas/ultraestrutura , Neoplasias Ovarianas/patologia , Distribuição Tecidual/efeitos dos fármacos , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Biomaterials ; 33(17): 4403-12, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22436800

RESUMO

A amphiphilic block copolymer composed of conventional monomethoxy (polyethylene glycol)-poly (d,l-lactide-co-glycolide)-poly (l-lysine) (mPEG-PLGA-b-PLL) was synthesized. The chemical structure of this copolymer and its precursors was confirmed by Fourier Transform Infrared Spectroscopy (FTIR), (1)H Nuclear Magnetic Resonance ((1)H NMR) and Gel Permeation Chromatography (GPC). The copolymer was used to prepare nanoparticles (NPs) that were then loaded with either the anti-cancer drug adriamycin or small interfering RNA-negative (siRNA) using a double emulsion method. MTT assays used to study the in vitro cytotoxicity of mPEG-PLGA-b-PLL NPs showed that these particles were not toxic in huh-7 hepatic carcinoma cells. Confocal laser scanning microscopy (CLSM) and flow cytometer analysis results demonstrated efficient mPEG-PLGA-b-PLL NPs-mediated delivery of both adriamycin and siRNA into the cells. In vivo the targeting delivery of adriamycin or siRNA mediated by mPEG-PLGA-b-PLL NPs in the huh-7 hepatic carcinoma-bearing mice was evaluated using a fluorescence imaging system. The targeting delivery results and froze section analysis confirmed that drug or siRNA is deliver to tumor more efficiently by mPEG-PLGA-b-PLL NPs than free drug or Lipofectamine™2000. The high efficiency delivery of mPEG-PLGA-b-PLL NPs mainly due to the enhancement of cellular uptake. These results imply that mPEG-PLGA-b-PLL NPs have a great potential to be used as an effective carriers for adriamycin or siRNA.


Assuntos
Doxorrubicina/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Técnicas de Transferência de Genes , Poliésteres/química , Polietilenoglicóis/química , Polilisina/análogos & derivados , RNA Interferente Pequeno/administração & dosagem , Aminas/química , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cromatografia em Gel , Doxorrubicina/farmacologia , Feminino , Citometria de Fluxo , Humanos , Hidroxilação/efeitos dos fármacos , Lisina/química , Espectroscopia de Ressonância Magnética , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Confocal , Microscopia de Fluorescência , Nanopartículas/toxicidade , Nanopartículas/ultraestrutura , Neoplasias/metabolismo , Neoplasias/patologia , Tamanho da Partícula , Poliésteres/síntese química , Polietilenoglicóis/síntese química , Polilisina/síntese química , Polilisina/química , Polimerização/efeitos dos fármacos , RNA Interferente Pequeno/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier
9.
Biomaterials ; 33(28): 6739-47, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22763223

RESUMO

Cyclic peptide (arginine-glycine-aspartic-glutamic-valine acid, cRGD)-modified monomethoxy (polyethylene glycol)-poly (D,L-lactide-co-glycolide)-poly (L-lysine) nanoparticles (mPEG-PLGA-PLL-cRGD NPs) with antitumor drug Mitoxantrone (DHAQ) or fluorescence agent Rhodamine B (Rb) encapsulated in their interior were prepared. The remarkable features of the mPEG-PLGA-PLL-cRGD NPs are the effective improvement for the cytotoxicity and uptake of the cell in vitro, and the significant enhancement of delivery ability for DHAQ or Rb in vivo. As a consequence, an excellent therapeutic efficiency for cancer is obtained, demonstrating the mPEG-PLGA-PLL-cRGD NPs play a key role in enhancing cancer therapeutic efficiency.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Portadores de Fármacos , Nanopartículas , Peptídeos Cíclicos , Poliésteres , Polietilenoglicóis , Polilisina/análogos & derivados , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitoxantrona/administração & dosagem , Mitoxantrona/química , Mitoxantrona/farmacocinética , Nanopartículas/administração & dosagem , Nanopartículas/química , Tamanho da Partícula , Peptídeos Cíclicos/administração & dosagem , Peptídeos Cíclicos/química , Poliésteres/administração & dosagem , Poliésteres/química , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Polilisina/administração & dosagem , Polilisina/química , Distribuição Tecidual
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA