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1.
Chem Commun (Camb) ; 57(71): 8961-8964, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34486587

RESUMO

Optical properties of anisotropic gold nanorod arrays inside anodic aluminium oxide substrates enhance the longitudinal absorption intensities and the hyperthermia cancer cell killing at 42.1 °C under photothermal laser exposures at 671 nm.


Assuntos
Antineoplásicos/farmacologia , Nanotubos/química , Terapia Fototérmica/métodos , Óxido de Alumínio/química , Óxido de Alumínio/farmacologia , Óxido de Alumínio/efeitos da radiação , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Morte Celular/fisiologia , Ouro/química , Ouro/farmacologia , Ouro/efeitos da radiação , Células HeLa , Humanos , Nanotubos/efeitos da radiação
2.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360814

RESUMO

This study aimed to develop a novel magnetic resonance imaging (MRI)-detectable boron (B)-containing nanoassemblies and evaluate their potential for boron neutron capture therapy (BNCT). Starting from the citrate-coated gold nanoparticles (AuNPs) (23.9 ± 10.2 nm), the diameter of poly (D, L-lactide-co-glycolide) AuNPs (PLGA-AuNPs) increased approximately 110 nm after the encapsulation of the PLGA polymer. Among various B drugs, the self-produced B cages had the highest loading efficiency. The average diameter of gadolinium (Gd)- and B-loaded NPs (PLGA-Gd/B-AuNPs) was 160.6 ± 50.6 nm with a B encapsulation efficiency of 28.7 ± 2.3%. In vitro MR images showed that the signal intensity of PLGA-Gd/B-AuNPs in T1-weighted images was proportional to its Gd concentration, and there exists a significantly positive relationship between Gd and B concentrations (R2 = 0.74, p < 0.005). The hyperintensity of either 250 ± 50 mm3 (larger) or 100 ± 50 mm3 (smaller) N87 xenograft was clearly visualized at 1 h after intravenous injection of PLGA-Gd/B-AuNPs. However, PLGA-Gd/B-AuNPs stayed at the periphery of the larger xenograft while located near the center of the smaller one. The tumor-to-muscle ratios of B content, determined by inductively coupled plasma mass spectrometry, in smaller- and larger-sized tumors were 4.17 ± 1.42 and 1.99 ± 0.55, respectively. In summary, we successfully developed theranostic B- and Gd-containing AuNPs for BNCT in this study.


Assuntos
Terapia por Captura de Nêutron de Boro/métodos , Boro/farmacologia , Gadolínio/farmacologia , Ouro/farmacologia , Nanopartículas Metálicas/uso terapêutico , Neoplasias/radioterapia , Nanomedicina Teranóstica/métodos , Animais , Linhagem Celular Tumoral , Humanos , Camundongos
3.
Int J Mol Sci ; 22(16)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34445294

RESUMO

Coupling of cells to biomaterials is a prerequisite for most biomedical applications; e.g., neuroelectrodes can only stimulate brain tissue in vivo if the electric signal is transferred to neurons attached to the electrodes' surface. Besides, cell survival in vitro also depends on the interaction of cells with the underlying substrate materials; in vitro assays such as multielectrode arrays determine cellular behavior by electrical coupling to the adherent cells. In our study, we investigated the interaction of neurons and glial cells with different electrode materials such as TiN and nanocolumnar TiN surfaces in contrast to gold and ITO substrates. Employing single-cell force spectroscopy, we quantified short-term interaction forces between neuron-like cells (SH-SY5Y cells) and glial cells (U-87 MG cells) for the different materials and contact times. Additionally, results were compared to the spreading dynamics of cells for different culture times as a function of the underlying substrate. The adhesion behavior of glial cells was almost independent of the biomaterial and the maximum growth areas were already seen after one day; however, adhesion dynamics of neurons relied on culture material and time. Neurons spread much better on TiN and nanocolumnar TiN and also formed more neurites after three days in culture. Our designed nanocolumnar TiN offers the possibility for building miniaturized microelectrode arrays for impedance spectroscopy without losing detection sensitivity due to a lowered self-impedance of the electrode. Hence, our results show that this biomaterial promotes adhesion and spreading of neurons and glial cells, which are important for many biomedical applications in vitro and in vivo.


Assuntos
Interfaces Cérebro-Computador , Neuroglia/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Titânio/farmacologia , Citoesqueleto de Actina/efeitos dos fármacos , Citoesqueleto de Actina/metabolismo , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Matriz Extracelular/química , Ouro/química , Ouro/farmacologia , Humanos , Teste de Materiais , Nanoestruturas/química , Neuritos/efeitos dos fármacos , Neuritos/fisiologia , Neuroglia/fisiologia , Neurônios/fisiologia , Compostos de Estanho/química , Compostos de Estanho/farmacologia , Titânio/química
4.
Molecules ; 26(16)2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34443657

RESUMO

Two ways to deliver ultrasmall gold nanoparticles and gold-bovine serum albumin (BSA) nanoclusters to the colon were developed. First, oral administration is possible by incorporation into gelatin capsules that were coated with an enteric polymer. These permit the transfer across the stomach whose acidic environment damages many drugs. The enteric coating dissolves due to the neutral pH of the colon and releases the capsule's cargo. Second, rectal administration is possible by incorporation into hard-fat suppositories that melt in the colon and then release the nanocarriers. The feasibility of the two concepts was demonstrated by in-vitro release studies and cell culture studies that showed the easy redispersibility after dissolution of the respective transport system. This clears a pathway for therapeutic applications of drug-loaded nanoparticles to address colon diseases, such as chronic inflammation and cancer.


Assuntos
Colo/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Nanopartículas Metálicas/química , Polímeros/farmacologia , Administração Oral , Cápsulas/química , Cápsulas/farmacologia , Gelatina/química , Gelatina/farmacologia , Ouro/química , Ouro/farmacologia , Humanos , Polímeros/química , Soroalbumina Bovina/química , Soroalbumina Bovina/farmacologia , Supositórios/química , Supositórios/farmacologia
5.
Int J Mol Sci ; 22(13)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34281198

RESUMO

Reconstruction of nerve defects is a clinical challenge. Autologous nerve grafts as the gold standard treatment may result in an incomplete restoration of extremity function. Biosynthetic nerve conduits are studied widely, but still have limitations. Here, we reconstructed a 10 mm sciatic nerve defect in healthy rats and analyzed nerve regeneration in poly (ε-caprolactone) (PCL) conduits longitudinally divided by gold (Au) and gold-cobalt oxide (AuCoO) nanoparticles embedded in poly-propylene poly-ethylene glycol (PPEG) membranes (AuPPEG or AuCoOPPEG) and compared it with unmodified PPEG-membrane and hollow PCL conduits. After 21 days, we detected significantly better axonal outgrowth, together with higher numbers of activated Schwann cells (ATF3-labelled) and higher HSP27 expression, in reconstructed sciatic nerve and in corresponding dorsal root ganglia (DRG) in the AuPPEG and AuCoOPPEG groups; whereas the number of apoptotic Schwann cells (cleaved caspase 3-labelled) was significantly lower. Furthermore, numbers of activated and apoptotic Schwann cells in the regenerative matrix correlated with axonal outgrowth, whereas HSP27 expression in the regenerative matrix and in DRGs did not show any correlation with axonal outgrowth. We conclude that gold and cobalt-oxide nanoparticle modified membranes in conduits improve axonal outgrowth and increase the regenerative performance of conduits after nerve reconstruction.


Assuntos
Ouro/administração & dosagem , Nanopartículas Metálicas/administração & dosagem , Regeneração Nervosa/efeitos dos fármacos , Nervo Isquiático/efeitos dos fármacos , Animais , Cobalto/farmacologia , Feminino , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Ouro/farmacologia , Nanopartículas Metálicas/química , Regeneração Nervosa/fisiologia , Óxidos/farmacologia , Poliésteres/química , Poliésteres/farmacologia , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Polipropilenos/química , Polipropilenos/farmacologia , Próteses e Implantes , Ratos , Ratos Wistar , Células de Schwann/efeitos dos fármacos , Células de Schwann/metabolismo , Nervo Isquiático/metabolismo
6.
Int J Nanomedicine ; 16: 4545-4557, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34267512

RESUMO

Background: Shigella infection has always been a global burden, and it particularly threatens children between the ages of 1 and 5 years. Economically underdeveloped countries are dominated by Shigella flexneri infection. The most effective method to treat Shigella is antibiotics, but with the abuse of antibiotics and the prevalence of multidrug resistance, we urgently need a relatively safe non-antibiotic treatment to replace it. Ultrasmall Au nanoclusters (NCs) have special physical and chemical properties and can better interact with and be internalized by bacteria to disrupt the metabolic balance. The purpose of this study was to explore whether Au NCs may be a substitute for antibiotics to treat Shigella infections. Methods: Au NCs and Shigella Sf301, R2448, and RII-1 were cocultured in vitro to evaluate the bactericidal ability of Au NCs. The degree of damage and mode of action of Au NCs in Shigella were clearly observed in images of scanning electron microscopy (SEM). In vivo experiments were conducted to observe the changes in body weight, clinical disease activity index (DAI) and colon (including length and histopathological sections) of mice treated with Au NCs. The effect of Au NCs was analysed by measuring the content of lipocalin-2 (LCN2) and Shigella in faeces. Next, the changes in Shigella biofilm activity, the release of reactive oxygen species (ROS), the changes in metabolism-related and membrane-related genes, and the effect of Au NCs on the body weight of mice were determined to further analyse the mechanism of action and effect. Results: Au NCs (100 µM) interfered with oxidative metabolism genes, induced a substantial increase in ROS levels, interacted with the cell membrane to destroy it, significantly killed Shigella, and effectively alleviated the intestinal damage caused by Shigella in mice. The activity of the biofilm formed by Shigella was reduced. Conclusion: The effective antibacterial effect and good safety suggest that Au NCs represent a good potential alternative to antibiotics to treat Shigella infections.


Assuntos
Colite/metabolismo , Colite/microbiologia , Ouro/química , Ouro/farmacologia , Nanopartículas Metálicas/química , Estresse Oxidativo/efeitos dos fármacos , Shigella/fisiologia , Animais , Colite/tratamento farmacológico , Ouro/uso terapêutico , Humanos , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Shigella/efeitos dos fármacos
7.
Int J Biol Macromol ; 185: 551-561, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34216657

RESUMO

Advanced melanoma patients that are not included in common genetic classificatory groups lack effective and safe therapeutic options. Chemotherapy and immunotherapy show unsatisfactory results and devastating adverse effects for these called triple wild-type patients. New approaches exploring the intrinsic antitumor properties of gold nanoparticles might reverse this scenario as a safer and more effective alternative. Therefore, we investigated the efficacy and safety of a composite made of gum arabic-functionalized gold nanorods (GA-AuNRs) against triple wild-type melanoma. The natural polymer gum arabic successfully stabilized the nanorods in the biological environment and was essential to improve their biocompatibility. In vivo results obtained from treating triple wild-type melanoma-bearing mice showed that GA-AuNRs remarkably reduced primary tumor growth by 45%. Furthermore, GA-AuNRs induced tumor histological features associated with better prognosis while also reducing superficial lung metastasis depth and the incidence of intrapulmonary metastasis. GA-AuNRs' efficacy comes from their capacity to reduce melanoma cells ability to invade the extracellular matrix and grow into colonies, in addition to a likely immunomodulatory effect induced by gum arabic. Additionally, a broad safety investigation found no evidence of adverse effects after GA-AuNRs treatment. Therefore, this study unprecedentedly reports GA-AuNRs as a potential nanomedicine for advanced triple wild-type melanomas.


Assuntos
Ouro/administração & dosagem , Goma Arábica/química , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Melanoma/tratamento farmacológico , Animais , Células 3T3 BALB , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Ouro/química , Ouro/farmacologia , Humanos , Neoplasias Pulmonares/metabolismo , Melanoma/metabolismo , Nanopartículas Metálicas , Camundongos , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Theranostics ; 11(15): 7589-7599, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34158868

RESUMO

Rational: Interstitial brachytherapy (BT) is a promising radiation therapy for cancer; however, the efficacy of BT is limited by tumor radioresistance. Recent advances in materials science and nanotechnology have offered many new opportunities for BT. Methods: In this work, we developed a biomimetic nanotheranostic platform for enhanced BT. Core-shell Au@AuPd nanospheres (CANS) were synthesized and then encapsulated in platelet (PLT)-derived plasma membranes. Results: The resulting PLT/CANS nanoparticles efficiently evaded immune clearance and specifically accumulated in tumor tissues due to the targeting capabilities of the PLT membrane coating. Under endoscopic guidance, a BT needle was manipulated to deliver appropriate radiation doses to orthotopic colon tumors while sparing surrounding organs. Accumulated PLT/CANS enhanced the irradiation dose deposition in tumor tissue while alleviating tumor hypoxia by catalyzing endogenous H2O2 to produce O2. After treatment with PLT/CANS and BT, 100% of mice survived for 30 days. Conclusions: Our work presents a safe, robust, and efficient strategy for enhancing BT outcomes when adapted to treatment of intracavitary and unresectable tumors.


Assuntos
Materiais Biomiméticos/farmacologia , Plaquetas , Braquiterapia , Ouro/farmacologia , Nanopartículas Metálicas/uso terapêutico , Neoplasias Experimentais/radioterapia , Paládio/farmacologia , Animais , Linhagem Celular Tumoral , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Células RAW 264.7
9.
Colloids Surf B Biointerfaces ; 205: 111899, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34098363

RESUMO

Intracellular bacterial infection is underlying many serious human disorders, leading to high morbidity and mortality. The development of safe and efficient therapeutic agents is the most effective solutions to combat intracellular bacterial infections. Recently, ultrasmall gold nanoclusters (AuNCs) have emerged as an innovative nanoantibiotics against multidrug-resistant bacterial infections due to their inherent antibacterial activity. However, the therapeutic effects of AuNCs on intracellular bacterial infections and their effects on host cells still remain unvisited. Here, we demonstrate the therapeutic potential of 4,6-diamino-2-mercaptopyrimidine-functionalized AuNCs (AuDAMP) for intracellular multidrug-resistant infections in a co-culture model of macrophages and methicillin-resistant Staphylococcus aureus (MRSA). The AuNCs were found to show a superior intracellular antibacterial capability, which can eliminate most of the MRSA phagocytosed by macrophages, and without exhibiting obvious cytotoxicity on host RAW 264.7 macrophages at tested concentrations. More importantly, treatment of AuDAMP exerts critical roles on enhancing the innate immune response to defend against pathogens invading inside the host cells and alleviating the bacterial infection-induced inflammatory response to avoid pyroptosis by up-regulating significantly xenophagy level in macrophages. Taken together, our results suggest that AuNCs hold great potential for the treatment of intracellular bacterial infections.


Assuntos
Infecções Bacterianas , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Farmacorresistência Bacteriana Múltipla , Ouro/farmacologia , Humanos , Imunidade Celular , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico
10.
ACS Appl Mater Interfaces ; 13(20): 23469-23480, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-33999610

RESUMO

Although photothermal therapy (PTT) has great potential for tumor inhibition, this single mode of action frequently encounters recurrence and metastasis, highlighting the urgent need for developing combination therapy. Inspired by established evidence that PTT could induce efficient immunogenic cell death (ICD), we here developed a versatile biomimetic nanoplatform (denoted as AuDRM) for the synergism of photothermal/starvation/immunotherapy against cancer. Specifically, dendritic mesoporous silica nanoparticles (NPs) were successfully constructed followed by the in situ synthesis of Au NPs in the mesopores. Afterward, a hybrid membrane was coated to facilitate the loading of R837. Upon efficient accumulation in the tumor tissue by homotypic targeting, the pH-sensitive membrane could be jettisoned to ensure the exposure of Au NPs for starvation therapy and the effective release of the immunostimulator R837 for enhancement of immunotherapy. Except for the PTT-mediated tumor ablation, the induction of ICD coupled with the release of tumor antigens could work synergistically with the immunostimulator R837 for inhibiting the primary tumor as well as the metastasis and induce a long-term immune memory effect for tumor inhibition via a vaccine-like function. Thus, this study paves the way for high-performance tumor ablation by the synergism of photothermal/starvation/immunotherapy.


Assuntos
Antineoplásicos/farmacologia , Ouro/química , Membranas Artificiais , Nanopartículas Metálicas/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Materiais Biomiméticos/química , Linhagem Celular Tumoral , Feminino , Ouro/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Imiquimode/química , Imiquimode/farmacocinética , Imiquimode/farmacologia , Imunoterapia , Nanopartículas Metálicas/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Fototerapia , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Life Sci ; 284: 119652, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34051217

RESUMO

AIMS: Gold nanoparticles (AuNPs) have been attracted interests in the various areas of clinical therapeutics. In this study, we investigated the anticancer and antiviral potential activity of AuNPs against influenza A virus and human glioblastoma (GMB) U-87 and U-251 cell lines. MAIN METHODS: Gold nanoparticles (AuNPs) were synthesized by citrate reduction method. Then, ultraviolet-visible spectrophotometry (UV-vis spectra) and electron microscopy analysis confirmed the type, size (mean diameter of 17 nm) and distribution of the particles. The AuNPs in vitro antiviral and anticancer effects was evaluated by hemagglutination inhibition (HAI), tissue culture infectious dose 50 (TCID50), real-time PCR, MTT, flow cytometry, and scratch assays. KEY FINDINGS: The AuNPs were synthesized in spherical with a mean diameter of 17 ± 2 nm and an absorbance peak at 520 nm. The AuNPs were well tolerable by MDCK cells at concentrations up to 0.5µg/ml and they significantly inhibited the hemagglutination and virus infectivity, particularly when added pre- or during virus infection. Furthermore, anticancer results indicated that AuNPs treatment caused the marked induction of apoptosis and reduced growth and migration capability of U-87 and U-251 cell lines in a time-dependent manner. SIGNIFICANCE: The present results suggest that AuNPs provide promising antiviral and anticancer approaches. Further research is needed to fully elucidate the mode of antiviral and anticancer action of AuNPs against influenza virus infection and human glioblastoma cell lines.


Assuntos
Antineoplásicos/farmacologia , Antivirais/farmacologia , Ouro/farmacologia , Nanopartículas Metálicas/química , Animais , Linhagem Celular Tumoral , Ensaios de Migração Celular , Cães , Glioblastoma/patologia , Ouro/toxicidade , Humanos , Células Madin Darby de Rim Canino , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/ultraestrutura
12.
J Mater Chem B ; 9(22): 4510-4522, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34027529

RESUMO

The development of highly integrated multifunctional nanomaterials with a superadditive therapeutic effect and good safety is an urgent but challenging task in cancer therapy research. The present study aims to design a nanoplatform that offers the opportunity to enhance antitumor activity while minimizing side effects. Given the Au-mediated X-ray radiation enhancement and the ability of Fe-based nanomaterials to create reactive oxygen species (ROS) and DNA damage, we anticipated that bimetallic Fe3O4-Au heterodimer would bring strong radiosensitizing capacity. Fe3O4-Au heterodimer surface was covered with bovine serum albumin (BSA) to achieve good surface functionality, stability and prolonged blood circulation. Folic acid (FA) moieties were added to the nanoformulation to increase tumor-homing, specificity and uptake. Finally, curcumin (CUR) was incorporated into the nanoparticle to function as a natural anticancer agent. The integration of all these components has yielded a single nanoplatform, Fe3O4-Au-BSA-FA-CUR, capable of successfully fulfilling the mission of superadditive cancer therapy to avoid the risks of organ removal surgery. The efficacy of the proposed nanoplatform was investigated in vitro and in vivo. High radiosensitizing ability, X-ray-induced ROS generation and DNA damage, and good biocompatibility were demonstrated through in vitro experiments. Also, the administration of Fe3O4-Au-BSA-FA-CUR with X-ray irradiation completely eradicated the tumor without any mortality and toxicity in healthy tissues in vivo. Our results highlight the potential of CUR-loaded Fe3O4-Au-BSA-FA heteronanostructure to enable synergistic localized radiochemotherapy and open up a new door to attractive possibilities that warrant further exploration.


Assuntos
Neoplasias da Mama/terapia , Compostos Férricos/farmacologia , Ouro/farmacologia , Radiossensibilizantes/farmacologia , Animais , Linhagem Celular Tumoral , Quimiorradioterapia , Camundongos
13.
Mater Sci Eng C Mater Biol Appl ; 124: 112035, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33947536

RESUMO

Biological applications of gold nanoparticles (AuNps) have potentially explored an efficient agent attributed to their biocompatibility and high efficiency in drug delivery. Our study applied an extract of Hibiscus syriacus L. callus (HCE) with a pioneer implementation on the induction of mass production. Bioactive compounds present in HCE were identified by Gas chromatography-mass spectrometry (GC-MS) and Liquid chromatography MS (LC-MS), wherein, the Denatonium was exclusively identifiable in HCE. Next, AuNps were synthesized and optimized using HCE (HCE-AuNps), and the comparison was conducted to evaluate the anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated macrophages. As per result, HCE-AuNps was reported to show a prominent reduction of pro-inflammatory cytokines and renovate the mitochondrial function through restoring the mitochondrial membrane potential changes, decreasing reactive oxygen species (ROS) accumulation, and recovering ATP contents, respectively. Furthermore, the immunoblotting of LC3b/a accumulation, and p62 rapid degradation revealed that HCE-AuNps could induce the autophagy as an intracellular response to reinforce alleviation of pro-inflammatory cytokines and mitochondria dysfunction. Besides, 740 Y-P (PI3K agonist) was used to verify that inhibiting autophagy could partially reverse HCE-AuNps suppressed mitochondrial dysfunction, and thus exacerbated inflammation, supporting a causal role for autophagy in the anti-inflammatory effect of HCE-AuNps. Taken together, we strongly anticipate that HCE-AuNps would act as a potential autophagy inducer for LPS-triggered macrophage's inflammation, providing a novel insight for biosynthetic nanoparticles in the treatment of mitochondria dysfunction and inflammation related diseases.


Assuntos
Hibiscus , Nanopartículas Metálicas , Anti-Inflamatórios/farmacologia , Autofagia , Ouro/farmacologia , Espécies Reativas de Oxigênio/farmacologia
14.
J Mater Chem B ; 9(13): 3025-3031, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33885664

RESUMO

The pharmacokinetics is a critical factor determining the clinical applicability of nanomaterials. Systematic study of the pharmacokinetics of functional nanomaterials is thus significant for promoting their applications. Herein, we take aminophenylboronic acid and mercaptophenylboronic acid-co-modified gold nanoparticles (A/M-Au NPs) with potent and tunable antibacterial activity as an example to study their behaviors in vitro and in vivo. The maximum concentration (Cmax, 2 mg L-1), the time to reach the maximum concentration (Tmax, 6 h), and the half-life (T1/2, 12 h) in the plasma of mice reflect appropriate pharmacokinetics of the gold nanoparticles as an ideal nano-antibiotic. Strikingly, the A/M-Au NPs show an extremely high median lethal dose (920 mg kg-1), which is about 100 times their effective dose (7.2 mg kg-1), suggesting their outstanding biosafety. The adequate pharmacokinetic profile and the high biosafety of the gold nanoparticles pave the way for their potential biomedical applications.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Ouro/farmacologia , Nanopartículas Metálicas/química , Animais , Antibacterianos/química , Pesquisa Biomédica , Células Cultivadas , Feminino , Ouro/química , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Tamanho da Partícula
15.
Eur J Med Chem ; 218: 113404, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-33823390

RESUMO

Cancer is the second leading cause of death worldwide. Cisplatin has challenged cancer treatment; however, resistance and side effects hamper its use. New agents displaying improved activity and more reduced side effects relative to cisplatin are needed. In this work we present the synthesis, characterization and biological activities of three complexes with quinoline-substituted 2,2':6',2″-terpyridine ligand: [Pt(4'-(2-quin)-terpy)Cl](SO3CF3) (1), [Au(4'-(2-quin)-terpy)Cl](PF6)2·CH3CN (2) and [Cu(4'-(2-quin)-terpy)Cl](PF6) (3). The three complexes displayed a high antiproliferative activity in ovarian carcinoma cell line (A2780) and even more noticeable in a colorectal carcinoma cell line (HCT116) following the order 3 > 2 > 1. The complexes IC50 are at least 20 × lower than the IC50 displayed by cisplatin (15.4 µM) in HCT116 cell line while displaying at the same time, much reduced cytotoxicity in a normal dermal fibroblast culture. These cytotoxic activities seem to be correlated with the inclination angles of 2-quin unit to the central pyridine. Interestingly, all complexes can interact with calf-thymus DNA (CT-DNA) in vitro via different mechanisms, although intercalation seems to be the preferred mechanism at least for 2 and 3 at higher concentrations of DNA. Moreover, circular dichroism (CD) data seems to indicate that complex 3, more planar, induces a high destabilization of the DNA double helix (shift from B-form to Z-form). Higher the deviation from planar, the lower the cytotoxicity displayed by the complexes. Cellular uptake may be also responsible for the different cytotoxicity exhibited by complexes with 3 > 2 >1. Complex 2 seems to enter cells more passively while complex 1 and 3 might enter cells via energy-dependent and -independent mechanisms. Complexes 1-3 were shown to induce ROS are associated with the increased apoptosis and autophagy. Moreover, all complexes dissipate the mitochondrial membrane potential leading to an increased BAX/BCL-2 ratio that triggered apoptosis. Complexes 2 and 3 were also shown to exhibit an anti-angiogenic effect by significantly reduce the number of newly formed blood vessel in a CAM model with no toxicity in this in vivo model. Our results seem to suggest that the increased cytotoxicity of complex 3 in HCT116 cells and its potential interest for further translation to pre-clinical mice xenografts might be associated with: 1) higher % of internalization of HCT116 cells via energy-dependent and -independent mechanisms; 2) ability to intercalate DNA and due to its planarity induced higher destabilization of DNA; 3) induce intracellular ROS that trigger apoptosis and autophagy; 4) low toxicity in an in vivo model of CAM; 5) potential anti-angiogenic effect.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Cobre/química , Cobre/farmacologia , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Ouro/química , Ouro/farmacologia , Humanos , Ligantes , Estrutura Molecular , Platina/química , Platina/farmacologia , Piridinas/química , Piridinas/farmacologia , Quinolinas/química , Quinolinas/farmacologia , Relação Estrutura-Atividade
16.
Eur J Med Chem ; 220: 113483, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-33915372

RESUMO

Three near-infrared (NIR-I) optical theranostic systems were synthesized, characterized and studied in vitro and in vivo. These original homo-bimetallic gold(I)-based aza-BODIPY complexes proved to be trackable through near-infrared optical imaging in cells and in mice. They display anti-proliferative properties in micromolar range against human and murine cancer cell lines (4T1, MDA-MB-231, CT26, and SW480). Moreover, the injection of the most promising theranostic agent in CT26 tumor-bearing BALB/c mice induced a significant anti-cancer activity.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Corantes Fluorescentes/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Compostos Aza/química , Compostos Aza/farmacologia , Compostos de Boro/química , Compostos de Boro/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Ouro/química , Ouro/farmacologia , Humanos , Raios Infravermelhos , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Imagem Óptica , Relação Estrutura-Atividade , Células Tumorais Cultivadas
17.
Sci Rep ; 11(1): 8692, 2021 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-33888738

RESUMO

A metal nanoparticle composite, namely TPNT1, which contains Au-NP (1 ppm), Ag-NP (5 ppm), ZnO-NP (60 ppm) and ClO2 (42.5 ppm) in aqueous solution was prepared and characterized by spectroscopy, transmission electron microscopy, dynamic light scattering analysis and potentiometric titration. Based on the in vitro cell-based assay, TPNT1 inhibited six major clades of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with effective concentration within the range to be used as food additives. TPNT1 was shown to block viral entry by inhibiting the binding of SARS-CoV-2 spike proteins to the angiotensin-converting enzyme 2 (ACE2) receptor and to interfere with the syncytium formation. In addition, TPNT1 also effectively reduced the cytopathic effects induced by human (H1N1) and avian (H5N1) influenza viruses, including the wild-type and oseltamivir-resistant virus isolates. Together with previously demonstrated efficacy as antimicrobials, TPNT1 can block viral entry and inhibit or prevent viral infection to provide prophylactic effects against both SARS-CoV-2 and opportunistic infections.


Assuntos
Ouro/farmacologia , Vírus da Influenza A Subtipo H1N1/fisiologia , Virus da Influenza A Subtipo H5N1/fisiologia , SARS-CoV-2/fisiologia , Prata/farmacologia , Óxido de Zinco/farmacologia , Enzima de Conversão de Angiotensina 2/metabolismo , Antivirais/química , Antivirais/farmacologia , Farmacorresistência Viral/efeitos dos fármacos , Aditivos Alimentares/farmacologia , Ouro/química , Células HEK293 , Humanos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Virus da Influenza A Subtipo H5N1/efeitos dos fármacos , Nanopartículas Metálicas/química , Nanocompostos/química , Oseltamivir/farmacologia , Tamanho da Partícula , Ligação Proteica/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos , Prata/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Internalização do Vírus/efeitos dos fármacos , Óxido de Zinco/química
18.
Int J Nanomedicine ; 16: 2789-2801, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33880024

RESUMO

Objective: Gold nanorods (AuNRs) show great potential for versatile biomedical applications, such as stem cell therapy and bone tissue engineering. However, as an indispensable shape-directing agent for the growth of AuNRs, cetyltrimethylammonium bromide (CTAB) is not optimal for biological studies because it forms a cytotoxic bilayer on the AuNR surface, which interferes with the interactions with biological cells. Methods: Citrate-stabilized AuNRs with various aspect-ratios (Cit-NRI, Cit-NRII, and Cit-NRIII) were prepared by the combination of end-selective etching and poly(sodium 4-styrenesulfonate)-assisted ligand exchange method. Their effects on osteogenic differentiation of the pre-osteoblastic cell line (MC3T3-E1), rat bone marrow mesenchymal stem cells (rBMSCs), and human periodontal ligament progenitor cells (PDLPs) have been investigated. Potential signaling pathway of citrate-stabilized AuNRs-induced osteogenic effects was also investigated. Results: The experimental results showed that citrate-stabilized AuNRs have superior biocompatibility and undergo aspect-ratio-dependent osteogenic differentiation via expression of osteogenic marker genes, alkaline phosphatase (ALP) activity and formation of mineralized nodule. Furthermore, Wnt/ß-catenin signaling pathway might provide a potential explanation for the citrate-stabilized AuNRs-mediated osteogenic differentiation. Conclusion: These findings revealed that citrate-stabilized AuNRs with great biocompatibility could regulate the osteogenic differentiation of multiple cell types through Wnt/ß-catenin signaling pathway, which promote innovative AuNRs in the field of tissue engineering and other biomedical applications.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Ácido Cítrico/farmacologia , Ouro/farmacologia , Nanotubos/química , Osteogênese/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Animais , Calcificação Fisiológica/efeitos dos fármacos , Células Cultivadas , Cetrimônio/farmacologia , Endocitose/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Nanotubos/ultraestrutura , Osteogênese/genética , Ligamento Periodontal/citologia , Ratos , Tiazolidinas/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos
19.
Int J Mol Sci ; 22(6)2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33803793

RESUMO

Inflammatory bowel diseases (IBD) are at the top of the worldwide rankings for gastrointestinal diseases as regards occurrence, yet efficient and side-effect-free treatments are currently unavailable. In the current study, we proposed a new concept for anti-inflammatory treatment based on gold (III) complexes. A new gold (III) complex TGS 121 was designed and screened in the in vitro studies using a mouse macrophage cell line, RAW264.7, and in vivo, in the dextran sulphate sodium (DSS)-induced mouse model of colitis. Physicochemical studies showed that TGS 121 was highly water-soluble; it was stable in water, blood, and lymph, and impervious to sunlight. In lipopolysaccharide (LPS)-stimulated RAW264.7 cells, the complex showed a potent anti-inflammatory profile, as evidenced in neutral red uptake and Griess tests. In the DSS-induced mouse model of colitis, the complex administered in two doses (1.68 µg/kg, intragastrically, and 16.8 µg/kg, intragastrically, once daily) produced a significant (* p < 0.05) anti-inflammatory effect, as shown by macroscopic score. The mechanism of action of TGS 121 was related to the enzymatic and non-enzymatic antioxidant system; moreover, TGS 121 induced changes in the tight junction complexes expression in the intestinal wall. This is the first study proving that gold (III) complexes may have therapeutic potential in the treatment of IBD.


Assuntos
Anti-Inflamatórios/uso terapêutico , Ouro/uso terapêutico , Inflamação/patologia , Intestinos/patologia , Estudo de Prova de Conceito , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Sulfato de Dextrana , Modelos Animais de Doenças , Ouro/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Células RAW 264.7 , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo
20.
Biochim Biophys Acta Rev Cancer ; 1875(2): 188532, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33667572

RESUMO

The present communication summarizes the importance, understanding and advancement in the photothermal therapy of cancer using gold nanoparticles. Photothermal therapy was used earlier as a single line therapy, but using a combination of photothermal therapy with other therapies like immunotherapy, chemotherapy, photodynamic therapy; efficient therapy management can be achieved. As it was discussed in many studies that gold nanoparticles are treated as idyllic photothermal transducers due to their structural dimensions, which enables them to strongly absorb near infrared light. Gold nanoparticles which are mediated for photothermal therapy can warn cancer cells to chemotherapy, regulate genes and immunotherapy by enhancing the cell permeability and intracellular delivery. The necrosis process and apoptosis depend on the power of laser and temperature within the cancerous tissues which are reached during irradiation. Cells death mechanism is also important because the cells which died through the process of necrosis can endorse secondary tumor growth while the cells which died through apoptosis may provoke the immune response to inhibit the development of secondary tumor growth. To decrease the in vivo barriers, gold nanostructures are again modified with targeting ligand and bio-responsive linker. The manuscript summarizes that the use of gold nanoparticles is capable of inhibiting the growth of cancerous cells by using photothermal therapy which has lesser adverse effects compared to other line therapies.


Assuntos
Ouro/farmacologia , Neoplasias/terapia , Terapia Fototérmica/métodos , Proliferação de Células/efeitos dos fármacos , Terapia Combinada , Ouro/química , Ouro/uso terapêutico , Humanos , Nanopartículas Metálicas
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