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1.
Chem Commun (Camb) ; 56(12): 1784-1787, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-31950129

RESUMO

Nanozymes have attracted extensive attention due to their great potential as alternatives to natural enzymes. Optical control as an external stimulus has become the most attractive method because of its high spatial and temporal resolution. Under the action of excitation light, free electrons on the surface of gold nanorods (GNRs) will collectively oscillate, which is called localized surface plasmon resonance (LSPR). This unique LSPR effect is promising in the application of plasmon-accelerated enzyme-like catalytic reactions. Pt-tipped gold nanorod-based nanozymes (Pt-GNRs) were synthesized by the modification of Pt nanoclusters onto the tips of GNRs. The as-prepared Pt-GNRs exhibited excellent enzyme-like catalytic activity toward hydrogen peroxide. Furthermore, it was found that the enzyme-like catalytic activity of Pt-GNRs could be notably enhanced using near-infrared (NIR) light irradiation, because of the photothermal effect and hot electron effect produced by the LSPR of GNRs. Finally, the catalytic activity and cytotoxicity of Pt-GNRs were evaluated in 4T1 cells, which further demonstrated that the Pt-GNR-based nanozymes possess great potential in cancer treatment.


Assuntos
Antineoplásicos/química , Ouro/química , Nanopartículas Metálicas/química , Platina/química , Ressonância de Plasmônio de Superfície , Antineoplásicos/farmacologia , Catálise , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Ouro/farmacologia , Humanos , Raios Infravermelhos , Platina/farmacologia , Relação Estrutura-Atividade
2.
Br J Radiol ; 93(1106): 20190742, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31778316

RESUMO

OBJECTIVE: One of the major issues in current radiotherapy (RT) is the normal tissue toxicity. A smart combination of agents within the tumor would allow lowering the RT dose required while minimizing the damage to healthy tissue surrounding the tumor. We chose gold nanoparticles (GNPs) and docetaxel (DTX) as our choice of two radiosensitizing agents. They have a different mechanism of action which could lead to a synergistic effect. Our first goal was to assess the variation in GNP uptake, distribution, and retention in the presence of DTX. Our second goal was to assess the therapeutic results of the triple combination, RT/GNPs/DTX. METHODS: We used HeLa and MDA-MB-231 cells for our study. Cells were incubated with GNPs (0.2 nM) in the absence and presence of DTX (50 nM) for 24 h to determine uptake, distribution, and retention of NPs. For RT experiments, treated cells were given a 2 Gy dose of 6 MV photons using a linear accelerator. RESULTS: Concurrent treatment of DTX and GNPs resulted in over 85% retention of GNPs in tumor cells. DTX treatment also forced GNPs to be closer to the most important target, the nucleus, resulting in a decrease in cell survival and increase in DNA damage with the triple combination of RT/ GNPs/DTX vs RT/DTX. Our experimental therapeutic results were supported by Monte Carlo simulations. CONCLUSION: The ability to not only trap GNPs at clinically feasible doses but also to retain them within the cells could lead to meaningful fractionated treatments in future combined cancer therapy. Furthermore, the suggested triple combination of RT/GNPs/DTX may allow lowering the RT dose to spare surrounding healthy tissue. ADVANCES IN KNOWLEDGE: This is the first study to show intracellular GNP transport disruption by DTX, and its advantage in radiosensitization.


Assuntos
Antineoplásicos/farmacologia , Docetaxel/farmacologia , Ouro/farmacologia , Nanopartículas Metálicas , Radiossensibilizantes/farmacologia , Antineoplásicos/farmacocinética , Transporte Biológico , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Docetaxel/farmacocinética , Sinergismo Farmacológico , Feminino , Ouro/farmacocinética , Células HeLa , Humanos , Radiossensibilizantes/farmacocinética , Neoplasias de Mama Triplo Negativas/radioterapia , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/radioterapia
3.
Int J Nanomedicine ; 14: 9007-9018, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819415

RESUMO

Background: Macrophages and Natural Killer (NK) cells are an integral part of the innate immune system. These cells produce pro-inflammatory cytokines in response to bacterial infections. However, prolonged inflammation can be a contributing factor in the etiology of several diseases such as rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, psoriasis and eczema. Reducing the secretion of pro-inflammatory cytokines is an effective treatment strategy for these conditions. Gold nanoparticles (AuNPs) have been shown to have immunosuppressive effects. Extracts of the Hypoxis hemerocallidea plant have also been shown to have immunomodulatory effects. It has been demonstrated previously that extracts of the H. hemerocallidea can be used to synthesize AuNPs. Purpose: This study aimed to investigate whether AuNPs synthesized using H. hemerocallidea extract and its major secondary metabolite, hypoxoside, have any immunomodulatory effects in macrophages and NK cells. Methodology: AuNPs derived from the H. hemerocallidea extract were synthesized as previously described. Using similar methodologies, this study shows for the first time the synthesis of AuNPs from hypoxoside. The AuNPs were characterized using several optical and spectroscopic techniques. The immunomodulatory effects of the aqueous extract of H. hemerocallidea, hypoxoside, as well as the AuNPs produced from the extract and hypoxoside, were investigated by measuring the cytokine levels in macrophages (IL-1ß, IL-6 and TNF-α) and NK cells (IFN-γ) using solid phase sandwich ELISA technique. Results: The results show that spherical AuNPs (average size 26 ± 2 nm) were synthesized from hypoxoside. The results also show that the four treatments (H. hemerocallidea extract, hypoxoside and their respective AuNPs can lower the pro-inflammatory cytokine levels in the macrophages cells, while only AuNPs produced from hypoxoside can reduce cytokine responses in NK cells. Conclusion: This study shows that all four treatments investigated here could be further explored for the development of anti-inflammatory therapies.


Assuntos
Alquinos/farmacologia , Glucosídeos/farmacologia , Ouro/farmacologia , Hypoxis/química , Fatores Imunológicos/farmacologia , Células Matadoras Naturais/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Nanopartículas Metálicas/química , Extratos Vegetais/química , Anti-Inflamatórios/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Humanos , Hidrodinâmica , Imunomodulação/efeitos dos fármacos , Nanopartículas Metálicas/ultraestrutura , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de Fourier , Células THP-1
4.
Int J Nanomedicine ; 14: 6843-6854, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692567

RESUMO

Purpose: Progression of chronic myeloid leukemia (CML) is frequently associated with increased angiogenesis at the bone marrow mediated by exosomes. The capability of gold nanoparticles (AuNPs) functionalized with antiangiogenic peptides to hinder the formation of new blood vessels has been demonstrated in a chorioallantoic membrane (CAM) model. Methods: Exosomes of K562 CML cell line were isolated and their angiogenic effect assessed in a CAM model. AuNPs functionalized with antiangiogenic peptides were used to block the angiogenic effect of CML-derived exosomes, assessed by evaluation of expression levels of key modulators involved in angiogenic pathways - VEGFA, VEGFR1 (also known as FLT1) and IL8. Results: Exosomes isolated from K562 cells promoted the doubling of newly formed vessels associated with the increase of VEGFR1 expression. This is a concentration and time-dependent effect. The AuNPs functionalized with antiangiogenic peptides were capable to block the angiogenic effect by modulating VEGFR1 associated pathway. Conclusion: Exosomes derived from blast cells are capable to trigger (neo)-angiogenesis, a key factor for the progression and spreading of cancer, in particular in CML. AuNPs functionalized with specific antiangiogenic peptides are capable to block the effect of the exosomes produced by malignant cells via modulation of the intrinsic VEGFR pathway. Together, these data highlight the potential of nanomedicine-based strategies against cancer proliferation.


Assuntos
Inibidores da Angiogênese/farmacologia , Exossomos/patologia , Ouro/farmacologia , Nanopartículas Metálicas/uso terapêutico , Neovascularização Patológica/tratamento farmacológico , Inibidores da Angiogênese/química , Animais , Embrião de Galinha , Membrana Corioalantoide/efeitos dos fármacos , Exossomos/metabolismo , Ouro/química , Humanos , Interleucina-8/metabolismo , Células K562/metabolismo , Nanopartículas Metálicas/química , Neovascularização Patológica/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo
5.
Artif Cells Nanomed Biotechnol ; 47(1): 4012-4019, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31591910

RESUMO

Gold nanoparticles (AuNPs) as the most excellent anticancer theranostic nanoparticles were synthesized through efficient, simple, and green synthesis method using Marsdenia tenacissima plant extracts and they are widely characterized by several techniques including ultraviolet-visible (UV) spectroscopy, atomic force microscopy (AFM), energy-dispersive X-ray spectrometers (EDS), transmission electron microscopy (TEM), and Fourier transform infrared (FT-IR) spectroscopy. From the AuNPs synthesized by M. tenacissima extracts, it was discovered that particle size around 50 nm, which is admirable nano dimension, was achieved by plant-mediated synthesis. After characterization of these nanoparticles, they performed as in vitro anticancer activity against lung cancer cell lines (A549). MTT assay revealed that AuNPs produce toxicity based on the dose-dependent A549 cells growth inhibition. AuNPs treatment activates caspase expression and down-regulates the anti-apoptotic protein expression in A549 cells. Our results point out that the AuNPs from M. tenacissima extract are apposite stabilizing agents, which serve as an effective anticancer agent against lung cancer cell lines (A549).


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ouro/química , Marsdenia/química , Nanopartículas Metálicas/química , Células A549 , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/genética , Proliferação de Células/efeitos dos fármacos , Ouro/farmacologia , Química Verde , Humanos , Neoplasias Pulmonares/patologia , Tamanho da Partícula , Extratos Vegetais/química , Extratos Vegetais/farmacologia
6.
Carbohydr Polym ; 225: 115228, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31521288

RESUMO

Developing new antibacterial nanomaterials and novel therapeutic strategies for the destruction of human pathogenic bacteria that cause infectious diseases is becoming more crucial, because infections caused by antibiotic-resistant bacteria are becoming more and more difficult to be effectively cured with commercially available antibiotics. In this study, we successfully developed new thiol chitosan-wrapped gold nanoshells (TC-AuNSs) as an antibacterial agent for the near-infrared (NIR) laser-triggered photothermal destruction of antibiotic-resistant pathogens, such as Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli), owing to their high water solubility, biocompatibility, strong NIR absorption, and outstanding photothermal properties. More interestingly, TC-AuNSs (115 µg/mL) were capable of completely destroying S. aureus, P. aeruginosa, and E.coli within 5 min of NIR laser irradiation, and no bacterial growth was detected on the tryptic soy agar (TSA) plate after 48 h of laser irradiation, indicating that TC-AuNSs along with laser irradiation are highly efficient and can kill bacteria quickly and prevent bacterial regrowth. We believe that TC-AuNSs deserve much more attention as an antibacterial agent, to be used in effectively combating pathogenic bacteria associated with public health problems and monitoring of environmental pollution for hygiene and safety.


Assuntos
Quitosana/farmacologia , Escherichia coli/efeitos dos fármacos , Ouro/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Infecções Bacterianas/terapia , Farmacorresistência Bacteriana/efeitos dos fármacos , Humanos , Lasers , Nanoconchas , Fototerapia
7.
Mater Sci Eng C Mater Biol Appl ; 104: 109909, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31499983

RESUMO

Redox-active quinones have been reported to show good potential for biological activities, while efforts are directed to explore the usefulness of these materials further in cancer management. Our previous study demonstrated that theaflavin and theaflavin-gallates (tea-extracted polyphenols) selectively induce apoptosis of tumour cells in vitro, but its concentration for showing half-maximal therapeutic response remains a matter of concern. In this report, we demonstrated that if theaflavin is conjugated with gold nanoparticles (AuNPs) to form a nanoconjugate AuNP@TfQ, its apoptotic ability increases significantly in comparison to the bare theaflavin (Tf). The nanoconjugate is prepared by following a one-step green synthesis ̶ a reaction between HAuCl4 and the aflavin at room temperature. AuNP@TfQ is characterized using particle size analysis, FESEM, UV-vis, FTIR, fluorescence, and X-ray photoelectron spectroscopytechniques. We assume that the enhanced anti-cancer effect of AuNP@TfQ appears due to the facile oxidation of the pristine theaflavin to its quinone derivative on the surface of AuNPs. The presence of quinone motif in AuNP@TfQ induces an increased level of ROS generation probably through the depolarization of mitochondria and resulted in the caspase-mediated apoptotic cell death which may hold the potential for a "magic bullet"-mediated ovarian cancer treatment.


Assuntos
Biflavonoides/farmacologia , Catequina/farmacologia , Ouro/farmacologia , Nanopartículas Metálicas/química , Neoplasias Ovarianas/patologia , Apoptose/efeitos dos fármacos , Biflavonoides/síntese química , Biflavonoides/química , Biomarcadores Tumorais/metabolismo , Catequina/síntese química , Catequina/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Endocitose/efeitos dos fármacos , Feminino , Hemólise/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Espectroscopia Fotoeletrônica , Espécies Reativas de Oxigênio/metabolismo
8.
ACS Appl Mater Interfaces ; 11(38): 34755-34765, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31474108

RESUMO

Radiation dosage constraints and hypoxia-associated resistance lead to the failure of radiotherapy (RT), especially in hypoxic liver cancer. Therefore, the intricate use of combined strategies for potentiating and complementing RT is especially important. In this work, we fabricated multifunctional Janus-structured gold triangle-mesoporous silica nanoparticles (NPs) as multifunctional platforms to deliver the hypoxia-activated prodrug tirapazamine (TPZ) for extrinsic radiosensitization, local photothermal therapy, and hypoxia-specific chemotherapy. The subsequent conjugation of folic acid-linked poly(ethylene glycol) provided the Janus nanoplatforms with liver cancer targeting and minimized opsonization properties. In vitro and in vivo experiments revealed the combined radiosensitive and photothermal antitumor effects of the Janus nanoplatforms. Importantly, the TPZ-loaded Janus nanoplatforms exhibited pH-responsive release behavior, which effectively improved the cellular internalization and therapeutic efficiency in hypoxic rather than normoxic liver cancer cells. Hypoxia-specific chemotherapy supplemented the ineffectiveness of radio-photothermal therapy in hypoxic tumor tissues, resulting in remarkable tumor growth inhibition without systematic toxicity. Therefore, our Janus nanoplatforms integrated radio-chemo-photothermal therapy in a hypoxia-activated manner, providing an efficient and safe strategy for treating liver cancer.


Assuntos
Quimiorradioterapia , Sistemas de Liberação de Medicamentos , Ouro , Hipertermia Induzida , Neoplasias Hepáticas Experimentais , Fototerapia , Pró-Fármacos , Dióxido de Silício , Tirapazamina , Animais , Hipóxia Celular , Linhagem Celular Tumoral , Ouro/química , Ouro/farmacologia , Humanos , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Neoplasias Hepáticas Experimentais/terapia , Camundongos , Camundongos Nus , Nanopartículas/química , Nanopartículas/uso terapêutico , Porosidade , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Tirapazamina/química , Tirapazamina/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
9.
ACS Appl Mater Interfaces ; 11(38): 34634-34644, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31475516

RESUMO

Intravenous (IV) route is the most commonly used drug-delivery approach. However, the targeting efficiency to tumor through IV delivery is usually less than 10%. To address this limitation, we report a new systemic delivery method utilizing injectable and quadruple-functional hydrogels to improve targeting efficiency through passive, active, and magnetic targeting, and hydrogel-controlled sustained release. The hydrogels consist of a folate/polyethylenimine-conjugated poly(organophosphazene) polymer, which encapsulates small interfering RNA (siRNA) and Au-Fe3O4 nanoparticles to form a nanocapsule (NC) structure by a simple mixing. The hydrogels are localized as a long-term "drug-release depot" after a single subcutaneous injection and sol-gel phase transition. NCs released from the hydrogels enter the circulatory systems and then target the tumor through enhanced permeability and retention/folate/magnetism triple-targeting, over the course of circulation, itself prolonged by the controlled release. In vivo experiments show that 12% of NCs are successfully delivered to the tumor, which is a considerable improvement compared to most results through IV delivery. The sustained targeting of gold to tumor enables two cycles of photothermal therapy, resulting in an enhanced silencing effect of siRNA and considerable reduction of tumor volume, which we are unable to achieve via simple intravenous injection.


Assuntos
Hidrogéis , Hipertermia Induzida , Neoplasias Experimentais , Fototerapia , Administração Intravenosa , Animais , Linhagem Celular Tumoral , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Feminino , Óxido Ferroso-Férrico/química , Óxido Ferroso-Férrico/farmacologia , Ouro/química , Ouro/farmacologia , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Neoplasias Experimentais/terapia , RNA Interferente Pequeno/química , RNA Interferente Pequeno/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
10.
ACS Appl Mater Interfaces ; 11(39): 35548-35555, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31483138

RESUMO

Overexpression of adenosine 5'-triphosphate-binding cassette transporters is one of the primary causes of drug resistance in cancer. Downregulating the expression of these transporters by inhibiting the mRNA translation process is an effective approach to cope up with this situation. Herein, multifunctional molecular beacons (MBs)-modified gold nanoparticle (AuNP) as a nanocarrier (MBs-AuNP) is developed for synergistic inhibition and in situ imaging of drug-resistant-related mRNAs in living cells. MBs-AuNP is composed of (i) triple specially designed molecular beacons modified on the surface of AuNP, for binding drug-resistant-related mRNAs, loading doxorubicin (Dox), and reporting the fluorescence signal, and (ii) AuNP, for loading MBs, introducing them into cells, and quenching their fluorescence. After uptake by cells, MBs-AuNP will hybridize with three different drug-resistant-related mRNAs (MDR1 mRNA, MRP1 mRNA, and BCRP mRNA), respectively, which could inhibit their translation to decrease efflux protein expression and lead to AuNP-quenched fluorescence recovery for in situ imaging. Real-time quantitative-polymerase chain reaction and western blot results showed that drug-resistant-related mRNAs and efflux proteins expression both decreased. Dox-loaded MBs-AuNP exhibited higher suppression efficacy compared to that of free Dox against HepG2/ADR (0.35 vs 1.06 µM of IC50) and MCF-7/ADR (2.78 vs >5 µM of IC50). Direct observation of intracellular hybridization events and differentiation of drug-resistant cancer cells or non-drug-resistant cancer cells could be accomplished through fluorescence imaging analysis. This nanocarrier is capable of downregulating the expression of multiple efflux proteins by gene silencing, allows in situ monitoring of silencing events, and thus provides a powerful strategy to cope up with drug resistance at the gene level.


Assuntos
Portadores de Fármacos , Resistencia a Medicamentos Antineoplásicos , Nanopartículas Metálicas/química , Imagem Molecular , RNA Mensageiro/metabolismo , RNA Neoplásico/metabolismo , Ouro/química , Ouro/farmacologia , Células Hep G2 , Humanos , Células MCF-7 , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo
11.
Int J Mol Sci ; 20(18)2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31514328

RESUMO

The effect of 15 nm-sized gold nanoparticles (AuNPs) and/or ionizing radiation (IR) on the migration and adhesion of human prostate (DU145) and lung (A549) cancer cell lines was investigated. Cell migration was measured by observing the closing of a gap created by a pipette tip on cell monolayers grown in 6-well plates. The ratio of the gap areas at 0 h and 24 h were used to calculate the relative migration. The relative migration of cells irradiated with 5 Gy was found to be 89% and 86% for DU145 and A549 cells respectively. When the cells were treated with 1 mM AuNPs this fell to ~75% for both cell lines. However, when the cells were treated with both AuNPs and IR an additive effect was seen, as the relative migration rate fell to ~60%. Of interest was that when the cells were exposed to either 2 or 5 Gy IR, their ability to adhere to the surface of a polystyrene culture plate was significantly enhanced, unlike that seen for AuNPs. The delays in gap filling (cell migration) in cells treated with IR and/or AuNPs can be attributed to cellular changes which also may have altered cell motility. In addition, changes in the cytoskeleton of the cancer cells may have also affected adhesiveness and thus the cancer cell's motility response to IR.


Assuntos
Movimento Celular/efeitos da radiação , Ouro/farmacologia , Neoplasias Pulmonares/patologia , Nanopartículas Metálicas/química , Neoplasias da Próstata/patologia , Radiação Ionizante , Adesão Celular/efeitos dos fármacos , Adesão Celular/efeitos da radiação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Endocitose , Humanos , Masculino
12.
Int J Nanomedicine ; 14: 5017-5032, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371944

RESUMO

Background: Epigallocatechin gallate (EGCG), the major anti-inflammatory compound in green tea, has been shown to suppress osteoclast (OC) differentiation. However, the low aqueous solubility of EGCG always leads to poor bioavailability, adverse effects, and several drawbacks for clinical applications. Purpose: In this study, we synthesized EGCG-capped gold nanoparticles (EGCG-GNPs) to solve the drawbacks for clinical uses of EGCG in bone destruction disorders by direct reduction of HAuCl4 in EGCG aqueous solution. Methods and Results: The obtained EGCG-GNPs were negatively charged and spherical. Theoretical calculation results suggested that EGCG was released from GNPs in an acidic environment. Cellular uptake study showed an obviously large amount of intracellular EGCG-GNPs without cytotoxicity. EGCG-GNPs exhibited better effects in reducing intracellular reactive oxygen species levels than free EGCG. A more dramatic anti-osteoclastogenic effect induced by EGCG-GNPs than free EGCG was observed in lipopolysaccharide (LPS)-stimulated bone marrow macrophages, including decreased formation of TRAP-positive multinuclear cells and actin rings. Meanwhile, EGCG-GNPs not only suppressed the mRNA expression of genetic markers of OC differentiation but also inhibited MAPK signaling pathways. Furthermore, we confirmed that EGCG-GNPs greatly reversed bone resorption in the LPS-induced calvarial bone erosion model in vivo, which was more effective than applying free EGCG, specifically in inhibiting the number of OCs, improving bone density, and preventing bone loss. Conclusion: EGCG-GNPs showed better anti-osteoclastogenic effect than free EGCG in vitro and in vivo, indicating their potential in anti-bone resorption treatment strategy.


Assuntos
Catequina/análogos & derivados , Ouro/farmacologia , Nanopartículas Metálicas/química , Osteogênese/efeitos dos fármacos , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Reabsorção Óssea/patologia , Catequina/farmacologia , Morte Celular/efeitos dos fármacos , Teoria da Densidade Funcional , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Ligantes , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Nanopartículas Metálicas/ultraestrutura , Camundongos Endogâmicos BALB C , Modelos Biológicos , Ligante RANK/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Crânio/patologia , Transcrição Genética/efeitos dos fármacos
13.
Artif Cells Nanomed Biotechnol ; 47(1): 3297-3305, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31379212

RESUMO

Siberian ginseng, perennial herb belongs to Araliaceae family used in traditional medicines to treat hypertension, thrombus, inflammation and cancer. In the present study, we biosynthesized goldnanoparticles using Siberian ginseng aqeous extract in a cost effective manner. The synthesized Siberian ginseng gold nanoparticle (SG-GNPs) were characterized using UV-Vis spec, HR-TEM, XRD, FTIR, SAED analysis. UV-Vis spectroscopic analysis showed a surface Plasmon resonance peak at 538 nm which does not reduce till 30 days of incubation. The results of HR-TEM, XRD and SAED confirm the spherical shape, crystalline nature and the size of the synthesized gold nanoparticles. The FTIR results prove that the biological components present in the Siberian ginseng had reduced the gold ions to synthesis gold nanoparticles. After characterization, the efficacy of SG-GNPS against the melanoma, a deadliest skin carcinoma, was assessed in vitro using B16 murine melanoma cells. The CC50 dose of SG-GNPs against B16 cells were assessed with MTT assay and the anticancer activity was evaluated using Rhodamine 123, H2DCFDA and dual staining techniques. The induction of apoptosis by SG-GNPs against melanoma cells were confirmed with q-PCR analysis. The results of staining techniques prove that SG-GNPs increase the reactive oxygen species and decreased the mitochondrial membrane potential. It is further confirmed by the results of q-PCR analysis which shows increased apoptotic Bid, Bad, Casp3, Casp 9 genes and decreased antiapoptotic Bcl2 gene expression in SG-GNPs treated cells. Our results authentically prove the biosynthesized SG-GNPs induces apoptosis in melanoma cells and it possesses anticancer property.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Eleutherococcus/química , Ouro/química , Ouro/farmacologia , Melanoma Experimental/patologia , Nanopartículas Metálicas , Animais , Antineoplásicos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ouro/metabolismo , Química Verde , Metaloproteinases da Matriz/metabolismo , Camundongos , Extratos Vegetais/metabolismo , Espécies Reativas de Oxigênio/metabolismo
14.
Int J Nanomedicine ; 14: 5323-5338, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409990

RESUMO

Background: Candida albicans as an opportunistic fungus is one of the most important causes of late-onset morbidity and mortality in patients with major burns and severely impaired immune system. In recent years, the emergence of resistance to opportunistic fungi and toxicity of antimicrobial drugs make it necessary to develop new drugs. Methods: In the present study, we investigated anticandidal effects of indolicidin, as a representative of host defense peptide, conjugated with gold nanoparticles in fluconazole-resistant clinical isolates of C. albicans. After characterizing the conjugation of indolicidin using biophysical methodologies, the cytotoxicity and hemolytic activity of the nanocomplex were examined. In addition, the expression level of ERG11, responsible for antifungal resistance, and the immunomodulatory effect of peptide-nanomaterial conjugates were assessed. Results: Our data indicated that the nanocomplex was nontoxic for the fibroblast cells and erythrocytes. Treatment with the nanocomplex significantly reduced the expression levels of the ERG11 gene in fluconazole-resistant C. albicans isolates and the iNOS gene in macrophages. Conclusion: The study data provides a chance to develop innovative therapies for the treatment of C. albicans burn infections. However, further investigation is required to examine the efficiency of the nanocomplex.


Assuntos
Antifúngicos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Queimaduras/microbiologia , Candida albicans/efeitos dos fármacos , Candida albicans/isolamento & purificação , Fluconazol/farmacologia , Ouro/farmacologia , Nanopartículas Metálicas/química , Animais , Peptídeos Catiônicos Antimicrobianos/química , Queimaduras/tratamento farmacológico , Candida albicans/genética , Morte Celular/efeitos dos fármacos , Farmacorresistência Fúngica/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Fluconazol/química , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Genes Fúngicos , Hemólise/efeitos dos fármacos , Humanos , Nanopartículas Metálicas/ultraestrutura , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Células NIH 3T3 , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo
15.
ACS Appl Mater Interfaces ; 11(37): 33659-33666, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31436085

RESUMO

Surface modification with oligonucleotides renders gold nanoparticles to endocytose through very different pathways as compared to unmodified ones. Such oligonucleotide-modified gold nanoparticles (OGNs) have been exploited as effective nanocarriers for gene regulation therapies. Notably, in an effort to reduce overall dosage and provide safer transition to the clinic, cooperative systems composed of two or more discrete nanomaterials have been recently proposed as an alternative to intrinsically multifunctional nanoparticles. Yet, our understanding of such systems designed to synergistically cooperate in their diagnostic or therapeutic functions remains acutely limited. Specifically, cellular interactions and uptake of OGNs are poorly understood when the cell simultaneously interacts with other types of nanoparticles. Here, we investigated the impact of simultaneous uptake of similar-sized iron oxide nanoparticles (IOPs) on the endocytosis and gene regulation function of OGNs, whose analogues have been proposed for sensitization, targeting, and treatment of tumors. We discovered that both the OGN uptake amount and, remarkably, the gene regulation function remained stable when exposed to a very wide range of extracellular concentrations of IOPs. Additionally, the co-localization analysis showed that a proportion of OGNs was co-localized with IOPs inside cells, which hints at the presence of similar trafficking pathways for OGNs and IOPs following endocytosis. Taken together, our observations indicate that while the OGN endocytosis is highly independent of the IOP endocytosis, it shares transport pathways inside cells-but does so without affecting the gene regulation behavior. These results provide key insights into concomitant interactions of cells with diverse nanoparticles and offer a basis for the future design and optimization of cooperative nanomaterials for diverse theranostic applications.


Assuntos
Portadores de Fármacos , Endocitose/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Ouro , Nanopartículas Metálicas , Oligonucleotídeos , Animais , Transporte Biológico Ativo/efeitos dos fármacos , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Ouro/química , Ouro/farmacocinética , Ouro/farmacologia , Células HeLa , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , Células NIH 3T3 , Oligonucleotídeos/química , Oligonucleotídeos/farmacocinética , Oligonucleotídeos/farmacologia
16.
ACS Appl Mater Interfaces ; 11(38): 34645-34651, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31448887

RESUMO

We have demonstrated that designed ankyrin repeat protein (DARPin) _9-29, which specifically targets human epidermal growth factor receptor 2 (HER2), binds tightly to gold mini nanorods (GNRs). Molecular dynamic simulations showed that a single layer of DARPin_9-29 molecules is formed on the surface of the nanorod and that conjugation with the nanorod does not involve the protein's domain responsible for specific binding to HER2. The nanorod-DARPin (DARPin-GNR) conjugate is specifically bound (in nanomolar concentrations) to human breast adenocarcinoma SK-BR-3 cells overexpressing HER2. Illumination by near-infrared light (850 nm) led to almost complete eradication of the conjugate-treated SK-BR-3 cells; the viability of epithelial human breast cancer cells expressing normal amounts of the receptor was much less affected by the illumination. The results reported here pave the way toward application of DARPin-GNR conjugates in phototherapy of cancer.


Assuntos
Adenocarcinoma , Neoplasias da Mama , Sistemas de Liberação de Medicamentos , Ouro , Nanopartículas Metálicas , Nanotubos/química , Fototerapia , Receptor ErbB-2/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Linhagem Celular Tumoral , Feminino , Ouro/química , Ouro/farmacologia , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico
17.
Nanoscale ; 11(35): 16336-16341, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31455962

RESUMO

The simultaneous possession of high tumor-targeting efficiency, long blood circulation, and low normal-tissue retention is critical for future clinically translatable nanomedicines. Herein, we reported a facile in situ glycoconjugation strategy for the synthesis of near-infrared (NIR)-emitting gold glyconanoparticles (AuGNPs, ∼2.4 nm) using 1-thio-ß-d-glucose as both the surface ligand and the reducing agent in the presence of a gold precursor. The ultrasmall AuGNPs showed similar low healthy organ retention to that of the renal-clearable ultrasmall nonglyconanoparticles, but ∼10 and 2.5 times higher in vitro and in vivo tumor-targeting efficiencies, respectively, were observed. This facile glycoconjugation strategy of ultrasmall AuGNPs was found to show activity towards glucose transporters in the cancer cells and prolonged blood circulation with both renal and hepatobiliary clearance pathways, which synergistically enhanced the tumor targeting of the ultrasmall AuGNPs. This discovery provides a smart strategy for the improvement in tumor targeting by ultrasmall NPs and further strengthens our understanding of glycoconjugation in designing future clinically translatable nanomedicines.


Assuntos
Sistemas de Liberação de Medicamentos , Corantes Fluorescentes , Glicoconjugados , Ouro , Nanopartículas Metálicas , Neoplasias Experimentais , Animais , Linhagem Celular Tumoral , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacocinética , Corantes Fluorescentes/farmacologia , Glicoconjugados/química , Glicoconjugados/farmacocinética , Glicoconjugados/farmacologia , Ouro/química , Ouro/farmacocinética , Ouro/farmacologia , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , Camundongos Nus , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo
18.
Artif Cells Nanomed Biotechnol ; 47(1): 3577-3584, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31456423

RESUMO

Gold nanoparticles (AuNPs) is the most excellent anticancer theranostic nanoparticles synthesized through efficient, simple and green synthesis method using extracts of Trichosanthes kirilowii, extensively characterized by UV-spectroscopy, FT-IR and TEM techniques. The AuNPs, synthesized by means of T. kirilowii extracts identified that nanoparticles were ∼50 nm in size, which is an admirable nano dimension attained by green synthesis. In agreement with the outcome of microscopic cellular morphological observations, MTT assay showed effective, selective, anticarcinogenic effect of AuNPs on HCT-116 cells in a dose-dependent manner. The AuNPs significantly enhance ROS generation, cause mitochondrial membrane damage and induce morphological changes using AO/EtBr staining assay. Furthermore, AuNPs treatment induces G0/G1 phase cell-cycle arrest in HCT-116 cells. Also, AuNPs treatment activates caspase expression and downregulates the anti-apoptotic expression in HCT-116 cells. Our results point out that the phytoconsituents isolated from T. kirilowii can act as appropriate reducing and stabilizing agents in the properties of AuNPs; hereby, it leads to the green synthesis of an anti-carcinogenic agent with highly efficient potential for cancer treatment.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias do Colo/patologia , Ouro/química , Ouro/farmacologia , Nanopartículas Metálicas , Trichosanthes/metabolismo , Anticarcinógenos/química , Anticarcinógenos/metabolismo , Anticarcinógenos/farmacologia , Ciclo Celular/efeitos dos fármacos , Ouro/metabolismo , Células HCT116 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos
19.
ACS Appl Mater Interfaces ; 11(38): 34717-34724, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31469541

RESUMO

The CRISPR/Cas gene editing system has been successfully applied to combating bacteria, cancer, virus, and genetic disorders. While viral vectors have been used for the delivery of the CRISPR/Cas9 system, the time required for insert cloning, and virus packaging and standardization, hinders its efficient use. Additionally, the high molecular weight of the Cas9 endonuclease makes it not easy for packing into the vehicles. Herein we report the self-assembly of gold nanoclusters (AuNCs) with SpCas9 protein (SpCas9-AuNCs) under physiological conditions and the efficient delivery of SpCas9 into the cell nucleus. This assembly process is highly dependent on pH. SpCas9-AuNCs are stable at a higher pH but are disassembled at a lower pH. Significantly, this assembly-disassembly process facilitates the delivery of SpCas9 into cells and the cell nucleus, where the SpCas9 exerts its cleavage function. As a proof-of-concept, the assembled SpCas9-AuNCs nanoparticles are successfully used for efficient knockout of the E6 oncogene, restoring the function of tumor-suppressive protein p53 and inducing apoptosis in cervical cancer cells with little effect on normal human cells. The SpCas9-AuNCs are useful for sgRNA functional validation, sgRNA library screening, and genomic manipulation.


Assuntos
Proteína 9 Associada à CRISPR , Genes Virais , Ouro , Nanopartículas Metálicas , Oncogenes , Proteína Supressora de Tumor p53/metabolismo , Neoplasias do Colo do Útero , Proteína 9 Associada à CRISPR/química , Proteína 9 Associada à CRISPR/farmacologia , Feminino , Ouro/química , Ouro/farmacologia , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/virologia
20.
ACS Appl Mater Interfaces ; 11(36): 32706-32719, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31411854

RESUMO

Overwhelming uncontrolled inflammation is the hallmark of pathophysiological features of many acute and chronic inflammatory diseases, such as sepsis and allergy and autoimmune disorders. It is important to develop potent pharmacological interventions to effectively control such detrimental inflammatory reactions in these diseases. Recently, we have developed a special class of peptide-gold nanoparticle hybrid system that can inhibit Toll-like receptor 4 (TLR4) signal transduction pathways and decrease its downstream inflammatory responses. Herein, we serendipitously discovered that a tiny amount of cigarette smoke extract (CSE, 1%) was able to significantly enhance the inhibitory activity of the hybrids on TLR4-mediated inflammatory responses. Mechanistically, it was found that active components in CSE were able to adsorb onto the hybrids and largely increased their cellular uptake in THP-1 cell-derived macrophages. Such high cellular uptake not only enhanced the inhibition on the endosomal acidification required for TLR4 activation but also contributed to autophagy induction and subsequent antioxidant protein expression. Consequently, this duel action strengthened the anti-inflammatory activity of the hybrids in cells and in an acute lung injury (ALI) mouse model. This work aids our fundamental understanding of nanoparticles regulating the innate immune responses. It also provides a new way to design potent anti-inflammatory nanotherapeutics for inflammatory diseases such as ALI.


Assuntos
Anti-Inflamatórios/farmacologia , Autofagia/efeitos dos fármacos , Ouro/farmacologia , Nanopartículas Metálicas/química , Peptídeos/farmacologia , Fumar , Receptor 4 Toll-Like/metabolismo , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/patologia , Animais , Anti-Inflamatórios/uso terapêutico , Heme Oxigenase-1/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/patologia , Masculino , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2 , Células THP-1
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