RESUMO
A new kind of core-crosslinked zwitterionic polymer nano aggregates was prepared by two steps: (1) terpolymers of lipoic acid, polyethylene glycol diglycidyl ether and l-lysine were prepared, forming nano aggregates with hydrodynamic radius of 80â¯nm-183â¯nm by self-assembly; (2) the crosslinking of the nano aggregates took place through a reaction of side chain group in lipoic acid structural unit with 1,4-dimercaptothreotol, producing zwitterionic polymer core-crosslinked nano aggregates. The aggregates were stable against dilution and protein adsorption, and they demonstrated good pH/redox dual-responsiveness due to the introduction of disulfide bonds and zwitterionic groups to the nano aggregates. Doxorubicin (DOX) was loaded into the nano aggregates for controlled release. The drug-loaded nano aggregates exhibited obvious pH and reduction sensitivities in response to the environmental conditions in tumor cells. The nano aggregates were biocompatible and could be potentially applied as anticancer drug vehicles for enhancement of cellular uptake of anticancer drugs.
Assuntos
Portadores de Fármacos/química , Nanoestruturas/química , Polímeros/química , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/metabolismo , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Íons/química , Lisina/química , Nanoestruturas/toxicidade , Oxirredução , Tamanho da Partícula , Polietilenoglicóis/química , Ácido Tióctico/químicaRESUMO
The polymeric micelles were prepared through a copolymerization of allyl polyethylene glycol (APEG) and N-isopropylacrylamide in the presence of 2-aminoethanethiol (AET), followed by a ring opening polymerization of γ-benzyl-l-glutamate N-carboxyanhydride (BLG-NCA). Doxorubicin (DOX) as a model drug was covalently conjugated into the core of micelles via hydrazone bonds. The drug loading capacity could reach up to 15% with drug encapsulation efficiency of 80%. The pH/thermo sensitivities were observed in the process of in vitro drug release. The DOX-loaded micelles exhibited accelerated drug release behaviors in an acidic condition, and enhanced therapeutic efficacy was observed. Furthermore, the cytotoxicity of micelles against Hela and 3T3 cells was evaluated before and after drug loading. The DOX-loaded micelles showed strong cytotoxic activity to the cancer cells. But the blank micelles showed non-cytotoxicity. Therefore, the thermo/pH dual-responsive polymeric micelles have a promising future applied as a controlled drug delivery system for anticancer drugs.
Assuntos
Preparações de Ação Retardada/farmacologia , Liberação Controlada de Fármacos , Micelas , Polímeros/química , Células 3T3 , Animais , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Polímeros/síntese química , Espectroscopia de Prótons por Ressonância Magnética , Espectroscopia de Infravermelho com Transformada de Fourier , TemperaturaRESUMO
Stimuli-responsive polymeric micelles were prepared through self-assembly of amphiphilic copolymers poly(ethylene glycol)-poly(γ-benzyl l-glutamate), followed by a core-crosslinking reaction using cystamine as the crosslinking agent. The crosslinked micelles with spherical morphologies in nanometer size showed enhanced stability against dilution and concentrated salt solutions compared to the micelles before crosslinking. Doxorubicin (DOX) as a model drug was encapsulated into the core of micelles through electrostatic interactions between carboxylic acid and DOX. In vitro drug release under pH and redox conditions was investigated. Furthermore, the cytotoxicity of micelles was evaluated before and after drug loading. The endocytosis of DOX-loaded micelles and the intracellular drug release were studied. DOX-loaded micelles exhibited accelerated drug release behaviors in an acidic and reductive environment, and showed an inhibited premature release behavior as compared to the noncrosslinked micelles. Considering their enhanced stability, pH and redox dual triggered responsive characteristics, the polymeric micelles can serve as potential systems for controlled drug delivery.
Assuntos
Preparações de Ação Retardada/farmacologia , Micelas , Polímeros/química , Células 3T3 , Animais , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Reagentes de Ligações Cruzadas/química , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Glutamatos/química , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Oxirredução , Tamanho da Partícula , Polímeros/síntese químicaRESUMO
The enhancement of tumor intracellular drug uptake and resistance against nonspecific protein adsorption are essential for an injectable anticancer drug carrier. In the present study, a new type of redox/pH-responsive zwitterionic nanoparticles (NPs) was prepared using poly-L-glutamic acid and cystamine in aqueous solutions under mild conditions. The NPs showed surface charge convertible feature in response to pH change of the solutions. The NPs demonstrated excellent anti nonspecific protein adsorption. In vitro release profiles of the NPs, they showed redox/pH dual sensitivities in vitro release. The effective intracellular delivery behaviors were verified through investigation of cell viability, and confocal laser scanning microscopy observation of HeLa cells after incubation with the DOX-loaded NPs. The NPs were non-cytotoxic and would have potential applications as a drug delivery vehicle for enhancing intracellular uptake of anticancer drugs.
Assuntos
Cistamina/química , Portadores de Fármacos/química , Nanopartículas/química , Ácido Poliglutâmico/química , Transporte Biológico , Preparações de Ação Retardada , Doxorrubicina/química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/toxicidade , Estabilidade de Medicamentos , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Espaço Intracelular/metabolismo , Teste de Materiais , Nanopartículas/toxicidade , Oxirredução , Propriedades de SuperfícieRESUMO
Hyperbranched polymer nano micelles (NMs) were prepared through a nucleophilic ring opening polymerization between cystamine and polyethylene glycol diglycidyl ether, followed by a reaction of amino groups and dimethyl maleic anhydride. The NMs showed spheric morphologies with hydrodynamic diameters of 106-120nm. Doxorubicin was loaded in the NMs with loading rate as high as 15.38wt%; The NMs possessed negative zeta potentials in aqueous solutions of pH7.4 due to the carboxyl ions on the particle surfaces, but the zeta potentials were converted to positive ones due to the hydrolysis of amide bonds at pH5.0-6.5, leading to the leaving of carboxyl groups and remaining of amino groups. The disulfide bonds in cystamine were designed in the hyperbranched polymer structures of the NMs, and bonds could be broken by a reducing agent l-glutathione (GSH) (10mM), resulting in a targeted drug release. The smart NMs displayed good biodegradability and biocompatibility, and they could be potentially used in drug controlled release field.
Assuntos
Liberação Controlada de Fármacos , Preparações de Ação Retardada , Doxorrubicina , Concentração de Íons de Hidrogênio , Micelas , Oxirredução , Polietilenoglicóis , PolímerosRESUMO
Terpolymers of poly (Lysine-co-N, N-Bis (acryloyl) cystamine-co-ß-Phenethylamine) (PLBP) were synthesized in one-pot by Michael addition terpolymerization. The terpolymers self-assembled into nano-sized spherical micelles (84-123nm) with narrow distributions. The surface charge of the nanomicelles (NMs) was depended on solution's pH and showed negative values under physiological conditions (pH7.4), which was beneficial for long circulation without non-specific protein adsorption. Doxorubicin (DOX) was effectively loaded into the NMs for controlled release. The in vitro release profiles exhibited obvious pH and reduction sensitivities in response to the environment mimicking tumor cells. The MTT assays demonstrated that blank NMs were biocompatible, and drug-laden NMs showed a significant cytotoxicity on Hela cells. The NMs could be potentially applied as smart drug delivery systems in cancer therapy.
Assuntos
Nanoestruturas , Preparações de Ação Retardada , Doxorrubicina , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Micelas , Oxirredução , FenetilaminasRESUMO
Zwitterionic nanoparticles have excellent serum stability. In this study, pH/redox responsive polymer was synthesized through a modification of dextran using succinic acid, followed by crosslinking with cystamine. The polymer could self-assemble into stable nanoparticles (NPs) in aqueous solution. The NPs carried certain amount of free carboxyl and amino groups on the surface, which endowed the NPs excellent anti-protein adsorption ability. The surface charge was negative at pH7.4 and was converted to positive at pH5.0. It was revealed that the NPs showed little non-specific protein adsorption and had excellent serum stability, and the NPs could be internalized in Hela cells rapidly. This result was ascribed to the charge reversible feature of the NPs. Doxorubicin (DOX) was loaded in the NPs for release studies in vitro. The DOX-loaded NPs exhibited obvious pH and reduction sensitivities in response to the environment in tumor cells due to the introduction of carboxyl groups, amino groups and disulfide bonds in the NPs. The NPs were biocompatible, biodegradable, and could be potentially applied as anticancer drug carriers for enhancement of tumor intercellular uptake of doxorubicin.
Assuntos
Doxorrubicina , Portadores de Fármacos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Células HeLa , Humanos , Neoplasias/metabolismo , Neoplasias/patologiaRESUMO
Zwitterionic copolymers have exhibited high resistance to nonspecific protein adsorption and have wide applications in drug delivery systems. Herein, a pH-responsive poly(Lysine-alt-N,N'-bis(acryloyl) diaminohexane) was synthesized through the Michael addition polymerization between N, N'-bis(acryloyl) diaminohexane and lysine. Subsequently, nano micelles (NMs) were formed by self-assembly of the copolymer in an aqueous solution. The NMs showed a slightly negative charge in blood environment, but a positively charged surface in extracellular pH of tumor. This feature could be used to enhance permeability and retention effect, and reinforce tumor cell uptake. Vitro release studies revealed that the release of DOX from the DOX-loaded NMs was evidently faster at pH 5.0 than at pH 7.4. MTT assays revealed that NMs were nontoxic. Thus, these smart NMs were feasible candidates and could be potentially used in cancer chemotherapy.
Assuntos
Resinas Acrílicas/química , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Micelas , Nanoestruturas/química , Polilisina/análogos & derivados , Polímeros/química , Células 3T3 , Resinas Acrílicas/síntese química , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Transporte Biológico , Bovinos , Preparações de Ação Retardada , Doxorrubicina/química , Doxorrubicina/metabolismo , Portadores de Fármacos/síntese química , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Espaço Intracelular/metabolismo , Camundongos , Polilisina/síntese química , Polilisina/química , Polímeros/síntese química , Propriedades de Superfície , Água/químicaRESUMO
To enhance drug cellular uptake, a biodegradable terpolymer is synthesized using taurine, N,N-Bis (acryloyl) cystamine, and dodecylamine as raw materials by Michael addition terpolymerization. The terpolymer is transformed to zwitterionic nanoparticles (NPs) through self-assembly. The surface charge of the NPs is convertible from negative at pH 7.4 to positive at pH 6.5, which endows the NPs' excellent nonfouling feature in bloodstream and effective uptake in tumor cells. The NPs display varied morphologies from solid micelles to polymersomes and nanorods depending on molar ratios of the structural units involved. The NPs can be biodegraded in l-glutathione (GSH) solution due to the split of disulfide bonds in main chains of the terpolymers. The NPs demonstrate good pH/reducing responsiveness in drug delivery and can be potentially used as anticancer drug vehicles for enhancement of cellular uptake of anticancer drug.
Assuntos
Antineoplásicos , Plásticos Biodegradáveis , Doxorrubicina , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Células 3T3 , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Plásticos Biodegradáveis/química , Plásticos Biodegradáveis/farmacocinética , Plásticos Biodegradáveis/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , CamundongosRESUMO
In this paper, a convenient and universal strategy is reported to fabricate high-resolution conducting polymer nanowires, combining edge nanoimprinting with gas etching. Based on this method, 81.3nm polypyrrole nanowires were obtained, which is much smaller than the original cavity. The resulting conducting polymer nanowires exhibit representative ohmic behavior and excellent sensitivity to NH3. This method may potentially be used to construct other organic nanoelectronic devices.
RESUMO
Peptide amphiphiles are capable of self-assembly into a diverse array of nanostructures including ribbons, tubes, and vesicles. However, the ability to select the morphology of the resulting structure is not well developed. We examined the influence of systematic changes in the number and type of hydrophobic and hydrophilic amino acids on the self-assembly of amphiphilic peptides. Variations in the morphology of self-assembled peptides of the form X(6)K(n) (X = alanine, valine, or leucine; K = lysine; n = 1-5) are investigated using a combination of transmission electron microscopy and dynamic light scattering measurements. The secondary structures of the peptides are determined using circular dichroism. Self-assembly is controlled through a combination of interactions between the hydrophobic segments of the peptide molecules and repulsive forces between the charged segments. Increasing the hydrophobicity of the peptide by changing X to a more lipophilic amino acid or decreasing the number of hydrophilic amino acids transforms the self-assembled nanostructures from vesicles to tubes and ribbons. Changes in the hydrophobicity of the peptides are reflected in changes in the critical micelle concentration observed using pyrene probe fluorescence analysis. Self-assembled materials formed from cationic peptide amphiphiles of this type display promise as carriers for insoluble molecules or negatively charged nucleic acids in drug or gene delivery applications.
Assuntos
Nanoestruturas , Peptídeos/química , Dicroísmo Circular , Microscopia Eletrônica de Transmissão , Tamanho da PartículaRESUMO
Monodispersed complex nano-particles were synthesized simply by mixing alginic acid (ALG-H) with poly[(2-dimethylamino) ethyl methacrylate] (PDEMA) in pure water without any surfactants or additives. The structure and properties of the nano-particles were extensively studied. The surface charges and average sizes of the nano-particles were varied with the composition of ALG-H and PDEMA. The nano-particles were formed through electrostatic attraction force, and they were very stable in pure water, but dissociated in salt solutions. An anticancer drug (doxorubicin) was loaded in the nano-particles and released in different saline solutions. The release profiles revealed that the drug release could be controlled by adjusting the pH and salt concentrations. The nano-particles displayed apparent advantages such as simple preparation process, low cost, free of organic solvents, size controllable, biodegradable and biocompatible.