Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.919
Filtrar
1.
Int J Mol Sci ; 22(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34445598

RESUMO

Intra-cellular active transport by native cargos is ubiquitous. We investigate the motion of spherical nano-particles (NPs) grafted with flexible polymers that end with a nuclear localization signal peptide. This peptide allows the recruitment of several mammalian dynein motors from cytoplasmic extracts. To determine how motor-motor interactions influenced motility on the single microtubule level, we conducted bead-motility assays incorporating surface adsorbed microtubules and combined them with model simulations that were based on the properties of a single dynein. The experimental and simulation results revealed long time trajectories: when the number of NP-ligated motors Nm increased, run-times and run-lengths were enhanced and mean velocities were somewhat decreased. Moreover, the dependence of the velocity on run-time followed a universal curve, regardless of the system composition. Model simulations also demonstrated left- and right-handed helical motion and revealed self-regulation of the number of microtubule-bound, actively transporting dynein motors. This number was stochastic along trajectories and was distributed mainly between one, two, and three motors, regardless of Nm. We propose that this self-regulation allows our synthetic NPs to achieve persistent motion that is associated with major helicity. Such a helical motion might affect obstacle bypassing, which can influence active transport efficiency when facing the crowded environment of the cell.


Assuntos
Movimento Celular , Citoplasma/metabolismo , Dineínas/metabolismo , Microtúbulos/metabolismo , Nanopartículas/metabolismo , Transporte Biológico , Transporte Biológico Ativo , Células HeLa , Humanos , Nanopartículas/química
2.
Int J Mol Sci ; 22(15)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34361049

RESUMO

Nanotechnology in the field of drug delivery comes with great benefits due to the unique physicochemical properties of newly developed nanocarriers. However, they may come as well with severe toxicological side effects because of unwanted accumulation in organs outside of their targeted site of actions. Several studies showed an unintended accumulation of various nanocarriers in female sex organs, especially in the ovaries. Some led to inflammation, fibrosis, or decreasing follicle numbers. However, none of these studies investigated ovarian accumulation in context to both reproductive aging and particle size. Besides the influences of particle size, the biodistribution profile may be altered as well by reproductive aging because of reduced capacities of the reticuloendothelial system (RES), changes in sex steroid hormone levels as well as altering ovarian stromal blood flow. This systematic investigation of the biodistribution of intravenously (i.v) injected nanoemulsions revealed significant dependencies on the two parameters particle size and age starting from juvenile prepubescent to senescent mice. Using fluorescent in vivo and ex vivo imaging, prepubescent mice showed nearly no accumulation of nanoemulsion in their uteri and ovaries, but high accumulations in the organs of the RES liver and spleen independently of the particle size. In fertile adult mice, the accumulation increased significantly in the ovaries with an increased particle size of the nanoemulsions by nearly doubling the portion of the average radiant efficiency (PARE) to ~10% of the total measured signal of all excised organs. With reproductive aging and hence loss of fertility in senescent mice, the accumulation decreased again to moderate levels, again independently of the particle size. In conclusion, the ovarian accumulation of these nanocarriers depended on both the age plus the particle size during maturity.


Assuntos
Envelhecimento/metabolismo , Nanopartículas/metabolismo , Ovário/metabolismo , Células 3T3 , Animais , Emulsões/administração & dosagem , Emulsões/farmacocinética , Emulsões/toxicidade , Feminino , Concentração Inibidora 50 , Injeções Intravenosas , Fígado/crescimento & desenvolvimento , Fígado/metabolismo , Camundongos , Nanopartículas/administração & dosagem , Nanopartículas/toxicidade , Ovário/crescimento & desenvolvimento , Baço/crescimento & desenvolvimento , Baço/metabolismo , Distribuição Tecidual
3.
ACS Appl Mater Interfaces ; 13(33): 39018-39029, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34397215

RESUMO

Targeting nanoparticles as drug delivery platforms is crucial to facilitate their cellular entry. Docking of nanoparticles by targeting ligands on cell membranes is the first step for the initiation of cellular uptake. As a model system, we studied brain microvascular endothelial cells, which form the anatomical basis of the blood-brain barrier, and the tripeptide glutathione, one of the most effective targeting ligands of nanoparticles to cross the blood-brain barrier. To investigate this initial docking step between glutathione and the membrane of living brain endothelial cells, we applied our recently developed innovative optical method. We present a microtool, with a task-specific geometry used as a probe, actuated by multifocus optical tweezers to characterize the adhesion probability and strength of glutathione-coated surfaces to the cell membrane of endothelial cells. The binding probability of the glutathione-coated surface and the adhesion force between the microtool and cell membrane was measured in a novel arrangement: cells were cultured on a vertical polymer wall and the mechanical forces were generated laterally and at the same time, perpendicularly to the plasma membrane. The adhesion force values were also determined with more conventional atomic force microscopy (AFM) measurements using functionalized colloidal probes. The optical trapping-based method was found to be suitable to measure very low adhesion forces (≤ 20 pN) without a high level of noise, which is characteristic for AFM measurements in this range. The holographic optical tweezers-directed functionalized microtools may help characterize the adhesion step of nanoparticles initiating transcytosis and select ligands to target nanoparticles.


Assuntos
Membrana Celular/metabolismo , Células Endoteliais/metabolismo , Glutationa/metabolismo , Nanopartículas/metabolismo , Pinças Ópticas , Fenômenos Biofísicos , Barreira Hematoencefálica/metabolismo , Encéfalo , Adesão Celular , Membrana Celular/ultraestrutura , Células Endoteliais/citologia , Galactosamina/química , Humanos , Ligantes , Microscopia de Força Atômica , Nanopartículas/química , Polietilenoglicóis/química , Polímeros/metabolismo , Propriedades de Superfície , Transcitose
4.
Chem Commun (Camb) ; 57(63): 7786-7789, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34264259

RESUMO

Herein, we propose a dual-responsive fluorescent nanoprobe to visualize the cross-talk between O2 and adenosine triphosphate (ATP) in living cells. We hope it will be a helpful tool for the further understanding of cellular metabolism and further facilitating risk warning in the process of adaptation to consistent environmental pressures in premalignant lesions.


Assuntos
Trifosfato de Adenosina/metabolismo , Corantes Fluorescentes/metabolismo , Nanopartículas/metabolismo , Oxigênio/metabolismo , Trifosfato de Adenosina/química , Corantes Fluorescentes/química , Humanos , Células MCF-7 , Nanopartículas/química , Oxigênio/química
5.
Int J Mol Sci ; 22(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198897

RESUMO

The introduction of metallic nanoparticles (mNPs) into the diet is a matter of concern for human health. In particular, their effect on the gastrointestinal tract may potentially lead to the increased passage of gluten peptides and the activation of the immune response. In consequence, dietary mNPs could play a role in the increasing worldwide celiac disease (CeD) incidence. We evaluated the potential synergistic effects that peptic-tryptic-digested gliadin (PT) and the most-used food mNPs may induce on the intestinal mucosa. PT interaction with mNPs and their consequent aggregation was detected by transmission electron microscopy (TEM) analyses and UV-Vis spectra. In vitro experiments on Caco-2 cells proved the synergistic cytotoxic effect of PT and mNPs, as well as alterations in the monolayer integrity and tight junction proteins. Exposure of duodenal biopsies to gliadin plus mNPs triggered cytokine production, but only in CeD biopsies. These results suggest that mNPs used in the food sector may alter intestinal homeostasis, thus representing an additional environmental risk factor for the development of CeD.


Assuntos
Doença Celíaca/dietoterapia , Dieta , Glutens/metabolismo , Nanopartículas/uso terapêutico , Biópsia , Células CACO-2 , Doença Celíaca/imunologia , Doença Celíaca/metabolismo , Doença Celíaca/patologia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/metabolismo , Homeostase/imunologia , Humanos , Imunidade/efeitos dos fármacos , Imunidade/imunologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Nanopartículas/metabolismo , Triticum/efeitos adversos
7.
AAPS PharmSciTech ; 22(5): 179, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34128132

RESUMO

With the limitation of solubility and dissolution rate of insoluble drugs, following oral administration, they would rifely prove poor and volatile bioavailability, which may fail to realize its therapeutic value. The drug nanocrystals are perceived as effective tactic for oral administration of insoluble drugs attributes to possess many prominent properties such as elevating dissolution rate and saturation solubility, high drug loading capacity, and improving oral bioavailability. Based on these advantages, the application of nanocrystals in oral drug delivery has acquired significant achievement, and so far more than 20 products of drug nanocrystals have been confirmed in the market. However, the oral absorption of drug nanocrystals is still facing huge challenges due to the limitation of many factors. Intrinsic properties of the drugs and complex physiological environment of the intestinal tract are the two most important factors affecting the oral bioavailability of drugs. In addition, the research on the multi-aspect mechanisms of nanocrystals promoting gastrointestinal absorption and bioavailability has been gradually deepened. In this review, we summarized recent advances of the nanocrystals delivered orally, and provided an overview to the research progress for crossing the intestinal tract transport mechanisms of the nanocrystals by some new research techniques. Meanwhile, the factors relevant to the transport of drug nanocrystals were also elaborated in detail. Graphical Abstract.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Absorção Intestinal/efeitos dos fármacos , Nanopartículas/administração & dosagem , Preparações Farmacêuticas/administração & dosagem , Administração Oral , Animais , Disponibilidade Biológica , Humanos , Absorção Intestinal/fisiologia , Nanopartículas/química , Nanopartículas/metabolismo , Preparações Farmacêuticas/química , Preparações Farmacêuticas/metabolismo , Solubilidade
8.
Int J Mol Sci ; 22(10)2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34069756

RESUMO

Hybrid nanostructures can be developed with inorganic nanoparticles (NPs) such as zinc oxide (ZnO) and natural antibacterials. ZnO NPs can also exert antibacterial effects, and we used them here to examine their dual action in combination with a natural antibacterial agent, protocatechuic acid (PCA). To produce hybrid nanoformulations, we functionalized ZnO NPs with four types of silane organic molecules and successfully linked them to PCA. Physicochemical assessment confirmed PCA content up to ~18% in hybrid nanoformulations, with a PCA entrapment efficiency of ~72%, indicating successful connection. We then investigated the in vitro release kinetics and antibacterial effects of the hybrid against Staphylococcus aureus. PCA release from hybrid nanoformulations varied with silane surface modification. Within 98 h, only 8% of the total encapsulated PCA was released, suggesting sustained long-term release. We used nanoformulation solutions collected at days 3, 5, and 7 by disc diffusion or log reduction to evaluate their antibacterial effect against S. aureus. The hybrid nanoformulation showed efficient antibacterial and bactericidal effects that also depended on the surface modification and at a lower minimum inhibition concentration compared with the separate components. A hybrid nanoformulation of the PCA prodrug and ZnO NPs offers effective sustained-release inhibition of S. aureus growth.


Assuntos
Hidroxibenzoatos/administração & dosagem , Hidroxibenzoatos/farmacologia , Óxido de Zinco/farmacologia , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Preparações de Ação Retardada/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana , Nanopartículas/química , Nanopartículas/metabolismo , Nanoestruturas/química , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Óxido de Zinco/química , Óxido de Zinco/metabolismo
9.
Arch Microbiol ; 203(7): 3893-3903, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34008070

RESUMO

Increasing environmental pollutants such as heavy metals have become one of the most severe health dangers because of rapid industrialization. Exposure to lead and nickel heavy toxic metals can lead to hazardous diseases affecting most of the organs in humans. Bioremediation is a process that uses the ability of microorganisms or plants to detoxify environmental contaminants at lower costs than physicochemical techniques. This study isolated halophilic bacteria from Khara salt lake in Iran and screened their ability to resist lead and nickel. After screening stages, three selected strains including Bacillus sp. A21, Oceanobacillus sp. A22 and Salinicoccus A43 were identified by16S rDNA sequencing and the related sequences were submitted to GeneBank with accession IDs MN588312, MN588313, and MN 588,314, respectively. These strains resist 7.2 mM, 4.1 mM, and 6.7 mM lead and 3.6 mM, 3.7 mM, and 4.1 mM nickel, respectively. Investigation of growth pattern and evaluation of bioremediation ability by atomic absorption spectroscopy revealed that Bacillus sp. A21 could decrease lead and nickel in culture medium up to 97.5% and 76%, respectively. Oceanobacillus sp. A22 showed higher lead bioremediation rate (98.8%) and lower nickel-bioremediation rate (73.5%). Salinicoccus sp. A43 showed the least bioremediation ability (92% lead and 71.7% nickel). The ability of selected strains to synthesize lead and nickel nanoparticles was evaluated using UV/Vis spectrophotometry and Energy-Dispersive X-ray Spectroscopy (EDX). Particle dimensions were measured using Scanning Electron Microscopy (SEM). Bacillus sp. A21 and Oceanobacillus sp. A22 strains were able to synthesize lead nanoparticles; however, Salinicoccus sp. A43 could synthesize both lead and nickel nanoparticles.


Assuntos
Bactérias , Biodegradação Ambiental , Metais Pesados , Nanopartículas , Bactérias/genética , Bactérias/metabolismo , Irã (Geográfico) , Lagos/microbiologia , Metais Pesados/metabolismo , Nanopartículas/química , Nanopartículas/metabolismo
10.
Bioconjug Chem ; 32(5): 1034-1046, 2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-33951913

RESUMO

SARS-CoV-2 caused the COVID-19 pandemic that lasted for more than a year. Globally, there is an urgent need to use safe and effective vaccines for immunization to achieve comprehensive protection against SARS-CoV-2 infection. Focusing on developing a rapid vaccine platform with significant immunogenicity as well as broad and high protection efficiency, we designed a SARS-CoV-2 spike protein receptor-binding domain (RBD) displayed on self-assembled ferritin nanoparticles. In a 293i cells eukaryotic expression system, this candidate vaccine was prepared and purified. After rhesus monkeys are immunized with 20 µg of RBD-ferritin nanoparticles three times, the vaccine can elicit specific humoral immunity and T cell immune response, and the neutralizing antibodies can cross-neutralize four SARS-CoV-2 strains from different sources. In the challenge protection test, after nasal infection with 2 × 105 CCID50 SARS-CoV-2 virus, compared with unimmunized control animals, virus replication in the vaccine-immunized rhesus monkeys was significantly inhibited, and respiratory pathology observations also showed only slight pathological damage. These analyses will benefit the immunization program of the RBD-ferritin nanoparticle vaccine in the clinical trial design and the platform construction to present a specific antigen domain in the self-assembling nanoparticle in a short time to harvest stable, safe, and effective vaccine candidates for new SARS-CoV-2 isolates.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Nanopartículas/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Linfócitos T/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Sítios de Ligação , Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , Ferritinas/química , Ferritinas/metabolismo , Imunidade Humoral , Macaca mulatta , Masculino , Nanopartículas/metabolismo , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/fisiologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T/metabolismo , Ultracentrifugação
11.
ACS Appl Mater Interfaces ; 13(20): 23396-23409, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-33982563

RESUMO

Paclitaxel (PTX) is a first-line chemotherapeutic drug for breast cancer, but PTX resistance often occurs in metastatic breast cancer. In addition, due to the poor targeting of chemotherapeutic drugs and the presence of the blood-brain barrier (BBB), it is hard to effectively treat brain metastatic breast cancer using paclitaxel. Thus, it is urgent to develop an effective drug delivery system for the treatment of brain metastatic breast cancer. The current study found that TWF1 gene, an epithelial-mesenchymal transition-associated gene, was overexpressed in brain metastatic breast cancer (231-BR) cells and was associated with the PTX resistance of 231-BR cells. Knockdown of TWF1 by small interference RNA (siRNA) in 231-BR cells could effectively increase the sensitivity of brain metastatic breast cancer cells to paclitaxel. Then, a liposome-based drug delivery system was developed for PTX delivery across BBB, enhancing PTX sensitivity and brain metastases targeting via BRBP1 peptide modification. The results showed that BRBP1-modified liposomes could effectively cross the BBB, specifically accumulate in brain metastases, and effectively interfere TWF1 gene expression in vitro and in vivo, and thus they enhanced proliferation inhibition, cell cycle arrest, and apoptosis induction, thereby inhibiting the formation and growth of brain metastases. In summary, our results indicated that BRBP1-modified and PTX- and TWF1 siRNA-loaded liposomes have the potential for the treatment of brain metastatic breast cancer, which lays the foundation for the development of a new targeted drug delivery system.


Assuntos
Neoplasias Encefálicas , Neoplasias da Mama/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Lipossomos , Paclitaxel , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/secundário , Linhagem Celular Tumoral , Feminino , Humanos , Lipossomos/química , Lipossomos/farmacocinética , Camundongos , Camundongos Endogâmicos BALB C , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Nanopartículas/química , Nanopartículas/metabolismo , Oligopeptídeos/química , Paclitaxel/química , Paclitaxel/farmacologia , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacocinética , RNA Interferente Pequeno/farmacologia
12.
ACS Appl Mater Interfaces ; 13(20): 23328-23338, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-33999598

RESUMO

With the failure of various amyloid-ß-targeted drugs for Alzheimer's disease (AD) in clinical trials, tau protein has gained growing attention as an alternative therapeutic target in recent years. The aggregation of tau exerts neurotoxicity, and its spreading in the brain is associated with increasing severity of clinical symptoms for AD patients; thus tau-targeting therapies hold great potential against AD. Here, a tau-targeted multifunctional nanoinhibitor based on self-assembled polymeric micelles decorated with tau-binding peptide is devised for AD treatment. Through the multivalent binding effect with the aggregating protein, this nanoinhibitor is capable of efficiently inhibiting tau protein aggregation, recognizing tau aggregates, and blocking their seeding in neural cells, thus remarkably mitigating tau-mediated cytotoxicity. Moreover, the formed nanoinhibitor-tau complex after binding is more easily degraded than mature tau aggregates, which will be conducive to enhance the therapeutic effect. We believe that this multifunctional nanoinhibitor will promote the development of new antitau strategies for AD treatment.


Assuntos
Doença de Alzheimer , Nanopartículas , Agregados Proteicos/efeitos dos fármacos , Proteínas tau , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Camundongos , Micelas , Nanomedicina , Nanopartículas/química , Nanopartículas/metabolismo , Proteínas tau/antagonistas & inibidores , Proteínas tau/química , Proteínas tau/metabolismo
14.
Proteins ; 89(9): 1065-1078, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33973262

RESUMO

SARS coronavirus 2 is neutralized by proteins that block receptor-binding sites on spikes that project from the viral envelope. In particular, substantial research investment has advanced monoclonal antibody therapies to the clinic where they have shown partial efficacy in reducing viral burden and hospitalization. An alternative is to use the host entry receptor, angiotensin-converting enzyme 2 (ACE2), as a soluble decoy that broadly blocks SARS-associated coronaviruses with limited potential for viral escape. Here, we summarize efforts to engineer higher affinity variants of soluble ACE2 that rival the potency of affinity-matured antibodies. Strategies have also been used to increase the valency of ACE2 decoys for avid spike interactions and to improve pharmacokinetics via IgG fusions. Finally, the intrinsic catalytic activity of ACE2 for the turnover of the vasoconstrictor angiotensin II may directly address COVID-19 symptoms and protect against lung and cardiovascular injury, conferring dual mechanisms of action unachievable by monoclonal antibodies. Soluble ACE2 derivatives therefore have the potential to be next generation therapeutics for addressing the immediate needs of the current pandemic and possible future outbreaks.


Assuntos
Enzima de Conversão de Angiotensina 2/química , Mimetismo Molecular , Receptores Virais/química , Receptores Virais/metabolismo , SARS-CoV-2/metabolismo , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Humanos , Fragmentos Fc das Imunoglobulinas/química , Fragmentos Fc das Imunoglobulinas/metabolismo , Mutação , Nanopartículas/química , Nanopartículas/metabolismo , Ligação Proteica , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , SARS-CoV-2/química
15.
Inorg Chem ; 60(10): 7475-7489, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-33939401

RESUMO

The biological enzyme-mimetic activity of cerium oxide nanoparticles (CeNPs) is well known to scavenge the reactive oxygen and nitrogen species in cell culture and animal models, imparting protection from the deleterious effects of oxidative and nitrosative stress. The superoxide dismutase (SOD)- and catalase-mimicking activity of CeNPs is reported to be controlled by the oxidation state of the surface "Ce" ions, where a high ratio of Ce3+/4+ or Ce4+/3+ has been considered for the displayed SOD and catalase-like activity, respectively. However, the redox behavior of CeNPs can be controlled by certain ligands that could offer changes in their enzyme-mimetic properties. Therefore, in this work, we have studied the enzyme-mimetic activities of CeNPs under the influence of polyoxometalates [phosphomolybdic acid (PMA) and phosphotungstic acid (PTA)], which are electron-dense molecules displaying quick and reversible multielectron redox reactions. Results revealed that the interaction of PMA with CeNPs results in the inhibition of the SOD-like activity; however, it has no impact on the catalase-like activity. Contrary to this, the interaction of PTA with CeNPs improved the SOD as well as catalase-like activities of CeNPs (3+), which generally do not exhibit catalase activity in the bare form. Although CeNPs (3+) did not show any peroxidase-like activity, CeNPs (4+) showed excellent activity, which was enhanced after the interaction with polyoxometalates. Further, the autoregeneration ability of CeNPs was found to be intact even after PTA or PMA interaction; however, the full catalytic activity was observed in the case of PTA but partially with PMA.


Assuntos
Cério/metabolismo , Nanopartículas/metabolismo , Superóxido Dismutase/metabolismo , Compostos de Tungstênio/metabolismo , Células Cultivadas , Cério/química , Humanos , Nanopartículas/química , Tamanho da Partícula , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/química , Propriedades de Superfície , Compostos de Tungstênio/química
16.
Chem Commun (Camb) ; 57(37): 4540-4543, 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33956004

RESUMO

Herein, we report the evaluation of dextran (DXT) derivatives bearing hydrophobic or hydrophilic functional groups as stabilisers of oil-in-water (O/W) emulsions. All investigated modifications conferred interfacial activity to produce stable O/W emulsions, methacrylate(MA)-functionalised DXT being the most promising stabiliser. A minimum amount of MA was required to obtain stable O/W nanoemulsions, which could be degraded in the presence of lipases.


Assuntos
Dextranos/metabolismo , Proteínas Fúngicas/metabolismo , Lipase/metabolismo , Nanopartículas/metabolismo , Óleos/metabolismo , Água/metabolismo , Dextranos/química , Emulsões/química , Emulsões/metabolismo , Proteínas Fúngicas/química , Interações Hidrofóbicas e Hidrofílicas , Lipase/química , Nanopartículas/química , Óleos/química , Tamanho da Partícula , Água/química
17.
Angew Chem Int Ed Engl ; 60(25): 14051-14059, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-33797161

RESUMO

Despite the promise of sonodynamic processes in cancer therapy, existing sonosensitizers often fail to regulate the generation of reactive oxygen species (ROS) against tumors, potentially leading to off-target toxicity to normal tissues. We report a transformable core-shell nanosonosensitizer (TiO2 @CaP) that reinvigorates ROS generation and dissolves its CaP shell to release Ca2+ in an acidic tumor microenvironment (TME) under ultrasound activation. Thus, TiO2 @CaP acts as a smart nanosonosensitizer that specifically induces mitochondrial dysfunction via overloading intracellular Ca2+ ions to synergize with the sonodynamic process in the TME. TiO2 @CaP substantially enhances immunogenic cell death, resulting in enhanced T-cell recruitment and infiltration into the immunogenic cold tumor (4T1). In conjunction with checkpoint blockade therapy (anti-PD 1), TiO2 @CaP-mediated sonodynamic therapy elicits systemic antitumor immunity, leading to regression of non-treated distant tumors and inhibition of lung metastasis. This work paves the way to development of "smart" TME-activatable sonosensitizers with temporospatial control over antitumor responses.


Assuntos
Neoplasias da Mama/metabolismo , Cálcio/metabolismo , Nanopartículas/metabolismo , Titânio/metabolismo , Terapia por Ultrassom , Animais , Neoplasias da Mama/terapia , Cálcio/química , Linhagem Celular Tumoral , Feminino , Camundongos , Nanopartículas/química , Tamanho da Partícula , Titânio/química , Microambiente Tumoral
18.
J Immunol ; 206(8): 1806-1816, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33811104

RESUMO

CD4+ T cells enable the critical B cell humoral immune protection afforded by most effective vaccines. We and others have recently identified an alternative source of help for B cells in mice, invariant NK T (iNKT) cells. iNKT cells are innate glycolipid-specific T cells restricted to the nonpolymorphic Ag-presenting molecule CD1d. As such, iNKT cells respond to glycolipids equally well in all people, making them an appealing adjuvant for universal vaccines. We tested the potential for the iNKT glycolipid agonist, α-galactosylceramide (αGC), to serve as an adjuvant for a known human protective epitope by creating a nanoparticle that delivers αGC plus antigenic polysaccharides from Streptococcus pneumoniae αGC-embedded nanoparticles activate murine iNKT cells and B cells in vitro and in vivo, facilitate significant dose sparing, and avoid iNKT anergy. Nanoparticles containing αGC plus S. pneumoniae polysaccharides elicits robust IgM and IgG in vivo and protect mice against lethal systemic S. pneumoniae However, codelivery of αGC via nanoparticles actually eliminated Ab protection elicited by a T-independent S. pneumoniae vaccine. This is consistent with previous studies demonstrating iNKT cell help for B cells following acute activation, but negative regulation of B cells during chronic inflammation. αGC-containing nanoparticles represent a viable platform for broadly efficacious vaccines against deadly human pathogens, but their potential for eliminating B cells under certain conditions suggests further clarity on iNKT cell interactions with B cells is warranted.


Assuntos
Linfócitos B/imunologia , Galactosilceramidas/metabolismo , Nanopartículas/metabolismo , Células T Matadoras Naturais/imunologia , Infecções Pneumocócicas/imunologia , Polissacarídeos Bacterianos/metabolismo , Vacinas Estreptocócicas/imunologia , Streptococcus pneumoniae/imunologia , Animais , Células Cultivadas , Galactosilceramidas/imunologia , Humanos , Imunidade Humoral , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Ativação Linfocitária , Camundongos , Polissacarídeos Bacterianos/imunologia , Linfócitos T/imunologia
19.
J Mater Chem B ; 9(18): 3838-3855, 2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-33908580

RESUMO

Although drug combination has proved to be an efficient strategy for clinic gastric cancer therapy, how to further improve their bioavailability and reduce the side effects are still challenges due to the low solubility and untargeted ability of drugs. Recently, newly emerging nanotechnology has provided an alternative for constructing new drug delivery systems with high targeting ability and solubility. In this study, a pH-responsive liposome (Liposome-PEO, LP) loaded with apatinib (AP) and cinobufagin (CS-1) was used for combinational therapy against gastric cancer after coating with a hybrid membrane (R/C). The results indicated that the constructed nanocomplex LP-R/C@AC not only efficiently killed tumor cells in vitro by inducing apoptosis, autophagy, and pyroptosis, but also significantly inhibited tumor invasion and metastasis via the VEGFR2/STAT3 pathway. Moreover, it showed stronger anti-tumor activity in gastric cancer-bearing mouse models, as compared to the sole drugs. A naturally-derived hybrid cell membrane coating bestowed nanocomplexes with enhanced biointerfacing including prolonged circulation time and targeting ability.


Assuntos
Antineoplásicos/farmacologia , Lipossomos/química , Nanopartículas/química , Transdução de Sinais/efeitos dos fármacos , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Materiais Biocompatíveis/química , Bufanolídeos/química , Bufanolídeos/farmacologia , Bufanolídeos/uso terapêutico , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Humanos , Camundongos , Camundongos Nus , Nanopartículas/metabolismo , Piridinas/química , Piridinas/farmacologia , Piridinas/uso terapêutico , Fator de Transcrição STAT3/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Distribuição Tecidual , Transplante Heterólogo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
20.
Phys Chem Chem Phys ; 23(15): 9158-9165, 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33885120

RESUMO

Nanoparticles (NPs) promise a huge potential for clinical diagnostic and therapeutic applications. However, nano-bio (e.g., the NP-cell membrane) interactions and underlying mechanisms are still largely elusive. In this study, two types of congeneric peptides, namely PGLa and magainin 2 (MAG2), with similar membrane activities were employed as model ligands for NP decoration, and the diffusion behaviours (including both translation and rotation) of the ligand-decorated NPs on a lipid bilayer membrane were studied via molecular dynamics simulations. It was found that, although both PGLa- and MAG2-coated NPs showed alternatively "hopping" and "jiggling" diffusions, the PGLa-coated ones had an enhanced circling at the hopping stage, while a much confined circling at the jiggling stage. In contrast, the MAG2-coated NPs demonstrated constant circling tendencies throughout the diffusion process. Such differences in the coupling between translational and rotational dynamics of these two types of NPs are ascribed to the different ligand-lipid interactions of PGLa and MAG2, in which the PGLa ligands prefer to vertically insert into the membrane, while MAG2 tends to lie flat on the membrane surface. Our results are helpful for the understanding the underlying associations between the NP motions and their interfacial membrane interactions, and shed light on the possibility of regulating NP behaviours on a cellular surface for better biomedical uses.


Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Proteínas Imobilizadas/metabolismo , Bicamadas Lipídicas/metabolismo , Magaininas/metabolismo , Nanopartículas/metabolismo , Peptídeos Catiônicos Antimicrobianos/química , Proteínas Imobilizadas/química , Ligantes , Bicamadas Lipídicas/química , Magaininas/química , Simulação de Dinâmica Molecular , Nanopartículas/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...