RESUMO
A dual-mode colorimetric and fluorometric sensor based on water soluble silver nanoclusters (AgNCs@PEI) is developed for quantitative and visual detection of ascorbic acid (Asc A). The detection method relies on the Asc A induced aggregation of AgNCs@PEI, which resulted in fluorecsence quenching of the sensor. The clusters exhibited a unique combination of static and collisional quenching with a wide range of dynamic detection (1-105 µM) Linear relationship was observed in the concentration range 102-103 µM using fluorescence and 0.2 × 102-5 × 103 µM using absorbance spectroscopy with respective detection limits of 10.65 µM and 2.49 µM. The corresponding colorimetric and fluorometric changes can be easily monitored by the naked eye with a visual detection limit of 103 µM. AgNCs@PEI were further integrated within a hydrogel for developing a solid-state visual detection platform. Notably, the sensing response of the clusters towards Asc A remained unaltered even after hydrogel integration. Additionally, digital image analysis was adopted, which improved the sensitivity of instrument-free fluorescence detection of Asc A. Analysis by the developed sensor showed excellent recovery percentages of Asc A in spiked urine samples, which further underscores the practical applicability of the sensor.
Assuntos
Colorimetria , Nanopartículas Metálicas , Colorimetria/métodos , Ácido Ascórbico/análise , Hidrogéis , Nanopartículas Metálicas/química , Limite de DetecçãoRESUMO
Biomaterial associated bacterial infections are indomitable to treatment due to the rise in antibiotic resistant strains, thereby triggering the need for new antibacterial agents. Herein, composite bactericidal hydrogels were formulated by incorporating silver nanotriangles (AgNTs) inside a hybrid polymer network of Gum Tragacanth/Sodium Alginate (GT/SA) hydrogels. Physico-chemical examination revealed robust mechanical strength, appreciable porosity and desirable in vitro enzymatic biodegradation of composite hydrogels. The antibacterial activity of AgNT-hydrogel was tested against planktonic and biofilm-forming Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria. For all the strains, AgNT-hydrogel showed a dose-dependent decrease in bacterial growth. The addition of AgNT-hydrogels (40-80 mg ml-1) caused 87% inhibition of planktonic biomass and up to 74% reduction in biofilm formation. Overall, this study proposes a promising approach for designing antibacterial composite hydrogels to mitigate various forms of bacterial infection.
Assuntos
Infecções Estafilocócicas , Tragacanto , Humanos , Prata/farmacologia , Prata/química , Hidrogéis/farmacologia , Hidrogéis/química , Tragacanto/química , Alginatos/farmacologia , Biofilmes , Bactérias , Escherichia coli , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
Peroxynitrite anion (ONOO-) is an important in vivo oxidative stress biomarker whose aberrant levels have pathophysiological implications. In this study, an electrochemical sensor for ONOO- detection was developed based on graphene nanoplatelets-cerium oxide nanocomposite (GNP-CeO2) incorporated polyaniline (PANI) conducting hydrogels. The nanocomposite-hydrogel platform exhibited distinct synergistic advantages in terms of large electroactive surface coverage and providing a conductive pathway for electron transfer. Besides, the 3D porous structure of hydrogel integrated the GNP-CeO2 nanocomposite to provide hybrid materials for the evolution of catalytic activity towards electrochemical oxidation of ONOO-. Various microscopic and spectroscopic characterization techniques endorsed the successful formation of GNP-CeO2-PANI hydrogel. Cyclic voltammetry (CV) measurements of GNP-CeO2-PANI hydrogel modified screen-printed electrodes (SPE) were carried out to record the current changes influenced by ONOO-. The prepared sensor demonstrated a significant dose-dependent increase in CV peak current within a linear range of 5-100 µM (at a potential of 1.12 V), and a detection limit of 0.14 with a sensitivity of 29.35 ± 1.4 µA µM-1. Further, a customized microfluidic flow system was integrated with the GNP-CeO2-PANI hydrogel modified SPE to enable continuous electrochemical detection of ONOO- at low sample volumes. The developed microfluidic electrochemical device demonstrated an excellent sensitivity towards ONOO- under optimal experimental conditions. Overall, the fabricated microfluidic device with hybrid hydrogels as electrochemical interfaces provides a reliable assessment of ONOO- levels. This work offers considerable potential for understanding the oxidative stress-related disease mechanisms through determination of ONOO- in biological samples.
Assuntos
Compostos de Anilina/metabolismo , Técnicas Eletroquímicas/métodos , Hidrogéis/metabolismo , Microfluídica/métodos , Ácido Peroxinitroso/metabolismoRESUMO
A fluorescent nanoprobe based on copper nanoclusters (CuNCs) has been developed for ratiometric detection of hydroxyl radicals (â¢OH) and superoxide anion radicals (O2â¢-). Two differently luminescent CuNCs, namely cyan-emissive poly(methacrylic acid)-protected copper nanoclusters (PCuNCs) and orange-emissive bovine serum albumin-protected CuNCs (BCuNCs), were conjugated to obtain a hybrid, dual-emission nanoprobe (PCuNCs-BCuNCs) with the corresponding peaks at 445 nm and 652 nm at an excitation wavelength of 360 nm. In particular, the fluorescence peak at 445 nm gradually enhanced with the incremental addition of â¢OH and O2â¢-. However, the fluorescence emission at 652 nm was greatly quenched in the presence of â¢OH, while in case of O2â¢-, the fluorescence intensity remained constant. The differential response of the PCuNCs-BCuNCs towards â¢OH and O2â¢- formed the basis of ratiometric detection. Under optimal conditions, the PCuNCs-BCuNCs exhibited good sensitivity and linearity towards â¢OH and O2â¢- with limits of detection of 0.15 µM and 1.8 µM, respectively. Moreover, the nanoprobe exhibited high selectivity for â¢OH and O2â¢- over other potential ROS interferences. Besides, PCuNCs-BCuNCs were eventually applied for qualitative and quantitative ratiometric assessment of intracellular â¢OH and O2â¢- in L-132 cells. Therefore, this strategy unveils a new potential for copper nanocluster-based sensing of ROS.
Assuntos
Corantes Fluorescentes/química , Radical Hidroxila/análise , Nanopartículas Metálicas/química , Superóxidos/análise , Animais , Bovinos , Cobre/química , Corantes Fluorescentes/síntese química , Células HeLa , Humanos , Limite de Detecção , Microscopia de Fluorescência/métodos , Ácidos Polimetacrílicos/química , Soroalbumina Bovina/química , Espectrometria de Fluorescência/métodosRESUMO
Despite recent advancements in the field of microfluidic paper-based analytical devices (µPADs), a key challenge remains in developing a simple and efficient µPAD with customized imaging capabilities for antioxidant assays. In the present study, we report a facile approach for µPAD fabrication through the application of transparent nail paint leading to creation of hydrophobic barriers and well-defined channels. The resultant µPADs were then characterized through scanning electron microscopy and contact angle measurements. The resolution and functional features of the fabricated µPAD were amenable to the intended assay. The µPAD's impregnated poly(methacrylic acid) (PMAA)-coated cerium oxide (CeO2) nanoparticles oxidized the 3,3',5,5'-tetramethylbenzidine (TMB) leading to the formation of a blue-colored charge-transfer complex. The addition of different antioxidant standard solutions resulted in a reduction in the blue color in a dose-dependent manner which could be observed visually. The color intensity of the PMAA-CeO2 nanoparticle@TMB oxidation product was inversely proportional to the antioxidant concentration and was measured using customized in-house MATLAB-based image processing software. Importantly, PMAA-CeO2 nanoparticle-based µPADs demonstrated good analytical characteristics and were able to be stored for long periods without any loss of activity. Moreover, potential interferents did not pose any threat to the colorimetric signal read-out for determination of antioxidant activity. The developed method was further applied for the assessment of antioxidant activity in a variety of tea samples and performed satisfactorily in comparison with a commonly used antioxidant detection method. Collectively, the developed µPAD-based platform holds great potential as a low-cost, convenient, portable and reliable method for pursuing various on-site antioxidant assays. Graphical Abstract.
Assuntos
Antioxidantes/farmacologia , Cério/química , Nanopartículas Metálicas/química , Técnicas Analíticas Microfluídicas/instrumentação , Ácidos Polimetacrílicos/química , Software , Interações Hidrofóbicas e Hidrofílicas , Oxirredução , Chá/químicaRESUMO
Nanoscale drug delivery systems have emerged as promising alternatives to overcome the problems associated with by conventional chemotherapy for cancer treatment such as poor drug stability and bio-distribution. Herein, we report a single walled carbon nanotubes (SWCNTs) based drug delivery system functionalized with polysaccharides such as alginate (ALG) and chitosan (CHI), which can be loaded with an anticancer drug curcumin (CUR). Modification of SWCNTs renders high drug loading efficiency and sustained drug release, imperative for drug activity. These were characterized through various tools viz, microscopic (transmission electron microscopy, scanning electron microscopy and atomic force microscopy) and zeta potential analysis. Incorporation of CUR inside the modified SWCNTs was studied through Fourier transform infrared spectroscopy, fluorescence and UV-visible spectroscopy. In vitro release studies were conducted to gain an insight into the pH-dependent release behavior of the entrapped CUR from modified SWCNTs. The anti-cancer potential was further demonstrated using human lung adenocarcinoma (A549) cells as a model system. Various cell culture based assays were performed to study the ability of released CUR from modified SWCNTs for inhibiting the cancer cell proliferation by inducing apoptosis.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/administração & dosagem , Curcumina/administração & dosagem , Portadores de Fármacos , Neoplasias Pulmonares/tratamento farmacológico , Nanotubos de Carbono , Adenocarcinoma de Pulmão , Sistemas de Liberação de Medicamentos , Humanos , Células Tumorais CultivadasRESUMO
In the present study, a facile one-step hydrothermal treatment of coriander leaves for preparing carbon dots (CDs) has been reported. Optical and structural properties of the CDs have been extensively studied by UV-visible and fluorescence spectroscopic, microscopic (transmission electron microscopy, scanning electron microscopy) and X-ray diffraction techniques. Surface functionality and composition of the CDs have been illustrated by elemental analysis and Fourier transform infrared spectroscopy (FTIR). Quenching of the fluorescence of the CDs in the presence of metal ions is of prime significance, hence CDs have been used as a fluorescence probe for sensitive and selective detection of Fe(3+) ions. Eventually, biocompatibility and bioimaging aspects of CDs have been evaluated on lung normal (L-132) and cancer (A549) cell lines. Qualitative analysis of cellular uptake of CDs has been pursued through fluorescence microscopy, while quantitative analysis using a flow cytometer provided an insight into the concentration and cell-type dependent uptake of CDs. The article further investigates the antioxidant activity of CDs. Therefore, we have validated the practicality of CDs obtained from a herbal carbon source for versatile applications.
Assuntos
Carbono/química , Técnicas de Química Analítica/instrumentação , Coriandrum/química , Imagem Molecular/métodos , Nanopartículas/química , Nanotecnologia/métodos , Folhas de Planta/química , Antioxidantes/síntese química , Antioxidantes/química , Antioxidantes/metabolismo , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Transporte Biológico , Linhagem Celular Tumoral , Técnicas de Química Sintética , Química Verde , Humanos , TemperaturaRESUMO
Noble metal nanoparticles incorporated in hybrid nanocomposites are considered as promising candidates for electrochemical applications owing to their physicochemical properties. In this work, we demonstrated the preparation of Fe2O3/rGO nanocomposite by hydrothermal method, followed by in situ Ag binding synthesis for the fabrication of hybrid nanocomposite (Ag/α-Fe2O3/rGO). The crystallographic structure of the hybrid nanocomposite is examined by X-ray diffraction (XRD) analysis which confirms the characteristics of Ag, Fe2O3, and rGO. The microscopic studies and energy-dispersive X-ray analysis (EDS) spectra confirmed the presence and formation of hybrid nanostructures. Raman analysis results further corroborate the formation of composite with significant D and G bands in Fe2O3/rGO and Ag/α-Fe2O3/rGO samples, which follow XRD results. Cyclic voltammetry (CV) and galvanostatic charge-discharge (GCD) studies were carried out to analyze the faradaic capacitor behavior. A specific capacitance of 209.09 F/g was observed by GCD studies for Ag/α-Fe2O3/rGO composites at a current density of 1 A/g, which exhibited good capacitance retention of 94% for 5000 cycles at 7 A/g. Furthermore, the Ag/α-Fe2O3/rGO electrode was used for the electrochemical detection of nitrate ions in soil by utilizing an ion-selective membrane over the surface of the Ag/α-Fe2O3/rGO electrode. The fabricated nanocomposite electrode showed a significant change in the peak current values with the concentration of nitrate in a linear range from 10 to 450 µM with the sensitivity to be calculated 1.426 µA µM-1 cm-2 and limit of detection (LOD) calculated to be 0.18 µM. The reproducibility and interference studies showed a promising result to be utilized for detecting nitrate ions in soil and in real-time applications.
Assuntos
Nanocompostos , Nitratos , Prata , Nanocompostos/química , Nitratos/química , Prata/química , Técnicas Eletroquímicas , Grafite/química , Compostos Férricos/química , Nanopartículas Metálicas/química , Capacitância ElétricaRESUMO
Biomedical implants are crucial for enhancing various human physiological functions. However, they are susceptible to microbial contamination after implantation, posing a risk of implant failure. To address this issue, hydrogel-based coatings are used, but achieving both effective antibacterial properties and stable adhesion remains challenging. This study introduces a hybrid hydrogel network made from Tannic Acid (TA) and Poly-l-Lysine (PLL), cross-linked through ionic and hydrogen bonds, which imparts adhesive and anti-infective properties. The physicochemical analysis revealed that the hydrogels exhibited significant porosity, favorable mechanical characteristics, and demonstrated in vitro enzymatic biodegradation. Moreover, the hydrogels demonstrated adhesion to various substrates, including Ti alloy with an adhesive strength of 42.5 kPa, and retained their integrity even after immersion in water for a minimum of 10 days. The modified Ti surfaces significantly reduced protein adsorption (â¼70 %), indicating antifouling properties. The hydrogels prevented bacterial adhesion on titanium surfaces through a "contact-kill" mode of action and inhibited biofilm formation by around 94.5 % for Staphylococcus aureus and 90.8 % for Pseudomonas aeruginosa. The modified Ti retained biofilm inhibitory effects for at least six days without significant performance decline. In vitro cytotoxicity assay confirmed the biocompatibility of the hydrogels with NIH3T3 cells. Overall, these results highlight the competence of hybrid hydrogels as effective coatings for Ti implants, offering strong adhesion and biofilm prevention to mitigate implant-related infections.
Assuntos
Antibacterianos , Biofilmes , Hidrogéis , Polilisina , Staphylococcus aureus , Taninos , Polilisina/química , Polilisina/farmacologia , Biofilmes/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Animais , Taninos/química , Taninos/farmacologia , Células NIH 3T3 , Staphylococcus aureus/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Titânio/química , Titânio/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Testes de Sensibilidade Microbiana , PolifenóisRESUMO
Skin tissue wound healing proceeds through four major stages, including hematoma formation, inflammation, and neo-tissue formation, and culminates with tissue remodeling. These four steps significantly overlap with each other and are aided by various factors such as cells, cytokines (both anti- and pro-inflammatory), and growth factors that aid in the neo-tissue formation. In all these stages, advanced biomaterials provide several functional advantages, such as removing wound exudates, providing cover, transporting oxygen to the wound site, and preventing infection from microbes. In addition, advanced biomaterials serve as vehicles to carry proteins/drug molecules/growth factors and/or antimicrobial agents to the target wound site. In this review, we report recent advancements in biomaterials-based regenerative strategies that augment the skin tissue wound healing process. In conjunction with other medical sciences, designing nanoengineered biomaterials is gaining significant attention for providing numerous functionalities to trigger wound repair. In this regard, we highlight the advent of nanomaterial-based constructs for wound healing, especially those that are being evaluated in clinical settings. Herein, we also emphasize the competence and versatility of the three-dimensional (3D) bioprinting technique for advanced wound management. Finally, we discuss the challenges and clinical perspective of various biomaterial-based wound dressings, along with prospective future directions. With regenerative strategies that utilize a cocktail of cell sources, antimicrobial agents, drugs, and/or growth factors, it is expected that significant patient-specific strategies will be developed in the near future, resulting in complete wound healing with no scar tissue formation.
Assuntos
Anti-Infecciosos , Materiais Biocompatíveis , Anti-Infecciosos/uso terapêutico , Materiais Biocompatíveis/uso terapêutico , Humanos , Estudos Prospectivos , Pele , CicatrizaçãoRESUMO
An alarming increase in implant failure incidence due to microbial colonization on the administered orthopedic implants has become a horrifying threat to replacement surgeries and related health concerns. In essence, microbial adhesion and its subsequent biofilm formation, antibiotic resistance, and the host immune system's deficiency are the main culprits. An advanced class of biomaterials termed anti-infective hydrogel implant coatings are evolving to subdue these complications. On this account, this review provides an insight into the significance of anti-infective hydrogels for preventing orthopedic implant associated infections to improve the bone healing process. We briefly discuss the clinical course of implant failure, with a prime focus on orthopedic implants. We identify the different anti-infective coating strategies and hence several anti-infective agents which could be incorporated in the hydrogel matrix. The fundamental design criteria to be considered while fabricating anti-infective hydrogels for orthopedic implants will be discussed. We highlight the different hydrogel coatings based on the origin of the polymers involved in light of their antimicrobial efficacy. We summarize the relevant patents reported in the prevention of implant infections, including orthopedics. Finally, the challenges concerning the clinical translation of the aforesaid hydrogels are described, and considerable solutions for improved clinical practice and better future prospects are proposed.
Assuntos
Anti-Infecciosos , Ortopedia , Anti-Infecciosos/uso terapêutico , Materiais Revestidos Biocompatíveis , Hidrogéis , Próteses e Implantes/efeitos adversosRESUMO
Nanotechnology driven cancer theranostics hold potential as promising future clinical modalities. Currently, there is a strong emphasis on the development of combinational modalities, especially for cancer treatment. In this study, we present a topical hydrogel patch for nanomaterial-assisted photothermal therapeutics as well as for on-demand drug delivery application. The patch was derived from interpenetrating networks (IPNs) of alginate (Alg) and polyacrylamide (PAAm) in weight ratio 8:1 by free radical polymerization. The patch interiors were composed of hybrid nanostructures derived from gold nanorods (AuNRs) anchored onto polyvinylpyrrolidone (PVP) functionalized graphene oxide (PVP-nGO) to form PVP-nGO@AuNRs hybrids. Field emission scanning electron microscopy (FE-SEM) images revealed the porous nature of the hybrid hydrogel patch with an average pore size of ~28.60 ± 3.10 µm. Besides, functional characteristics of the hybrid patch, such as mechanical strength, viscoelastic and swelling behavior, were investigated. Under near-infrared (NIR) radiation exposure, the hybrid patch exhibited photothermal properties such as surface temperature rise to 75.16 ± 0.32 °C, sufficient to ablate cancer cells thermally. Besides, the heat generated in the hybrid patch could be transmitted to an underlying hydrogel (mimicking skin tissue) when stacked together without much loss. Under cyclic photothermal heating, the patch could retain its photothermal stability for four cycles. Furthermore, the hybrid patch demonstrated NIR stimulated drug release, which was evaluated using methotrexate (MTX, water-insoluble anticancer drug) and rhodamine B (RhB, water-soluble dye). Taken together, this work provides a new dimension towards the development of externally placed hydrogel patches for thermal destruction of localized solid tumors and tunable delivery of chemotherapeutic drugs at the target site.
Assuntos
Portadores de Fármacos/química , Hidrogéis/química , Raios Infravermelhos , Alginatos/química , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Ouro/química , Grafite/química , Metotrexato/química , Metotrexato/metabolismo , Nanoestruturas/química , Nanotubos/química , Povidona/química , Reologia , Rodaminas/química , Rodaminas/metabolismo , TemperaturaRESUMO
Vehicle-generated toxic pollutants are composed of gaseous smoke and particulate byproducts accumulated as a black substance at its exhaust. This particulate matter (soot) is utilized for the green synthesis of highly stable, non-toxic, environment friendly, carbon quantum dots (CQD). The CQDs are synthesized via the simple hydrothermal route in the absence (C1) and presence (C2) of oxidants. The as-synthesized CQDs are amine functionalized using ethylenediamine. The amine functionalized CQDs (C1N and C2N) are explored for trinitrotoluene detection. From transmission electron microscopy, the average size of C1 and C2 was found to be about 4.2 nm and 5.6 nm respectively. The incorporation of amine groups lead to an increase in quantum yields from 5.63% to 12.7% for C1 and from 3.25% to 8.48% for C2 QDs. A limit of detection (LOD) of 13 ppb was displayed by C1N while the LODs of 11 ppb and 4.97 ppb were delivered by C2N at λ ex 370 nm and λ ex 420 nm respectively. The Stern-Volmer constant for C1N is 2.02 × 106 M-1 while for C2N at λ ex 370 nm and λ ex 420 nm is 0.38 × 106 M-1 and 0.48 × 106 M-1 respectively. Furthermore, C1N presents high selectivity for TNT compared to C2N. Owing to their higher luminescence, C1N particles are successfully demonstrated for their applicability in intracellular TNT detection.
RESUMO
A series of 1,8-naphthalimide-based fluorophores containing different chromophores with varying conjugation and electron richness at the imidic nitrogen atom are synthesized and characterized. These amine-functionalized naphthalimides are bipolar in nature and exhibit interesting optical and morphological variations attributable to the nature of the N substituents. Despite the fact that the dyes are structurally different owing to variation of the substituent on the imidic nitrogen atom, their electronic characteristics are similar and originate from the 4-aminonaphthalimide segment. Nevertheless, they exhibit variations in morphology in the microscopic domain, and this is attributable to structural differences. Further, these fluorescent dyes display biocompatibility and are used in the bioimaging of cells.
Assuntos
Materiais Biocompatíveis/química , Técnicas Eletroquímicas , Corantes Fluorescentes/química , Naftalimidas/química , Imagem Óptica , Materiais Biocompatíveis/síntese química , Linhagem Celular Tumoral , Corantes Fluorescentes/síntese química , Humanos , Naftalimidas/síntese química , Tamanho da Partícula , Processos Fotoquímicos , Teoria Quântica , TemperaturaRESUMO
Multifunctional hydrogels offer a seemingly efficient system for delivery of drugs and bioimaging modalities. The present study deals with the facile development of chitosan-based hydrogel formulation composed of highly fluorescent carbon dots (CDs) and loaded with a model anticancer drug, 5-Fluorouracil (5-FU). Herein, CDs were embedded firmly within the hydrogel matrices (CD-HY) via non-covalent interactions during the ionic cross-linking reaction. Furthermore, these hydrogels could effectively encapsulate 5-FU through hydrophobic interactions to form 5-FU@CD-HY. In this way, it was possible to combine the merits of both CDs and 5-FU on a common platform for monitoring the cellular uptake as well as therapeutic effects. Field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) illustrated the porous nature and formation of 5-FU@CD-HY. Besides, functional characteristics of 5-FU@CD-HY such as surface area, mechanical strength, swelling behavior and drug release were investigated. In vitro studies revealed the multifunctional aspects of 5-FU@CD-HY in monitoring the cellular uptake and inflicting apoptosis in A549 cells. Green fluorescence of CDs in 5-FU@CD-HY aided the qualitative and quantitative assessment of cellular uptake. In addition to this, the fluorescence of CDs could be used to detect apoptosis instigated by 5-FU, eliminating the need for multiplex dyes. Induction of apoptosis in 5-FU@CD-HY treated cells was evidenced by changes in cell cycle distributions and visualization of characteristic apoptotic bodies through FE-SEM. Apoptotic gene expression studies further elucidate the molecular mechanism involved in eliciting apoptosis. Thus, hydrogels mediated integration of fluorescent CDs with chemotherapeutic agents provides a new dimension for the potential use of hydrogels in cancer theranostics.
Assuntos
Apoptose/efeitos dos fármacos , Carbono/química , Fluoruracila/farmacologia , Hidrogéis/química , Polímeros/química , Células A549 , Animais , Antimetabólitos Antineoplásicos/química , Antimetabólitos Antineoplásicos/farmacocinética , Antimetabólitos Antineoplásicos/farmacologia , Proteínas Reguladoras de Apoptose/genética , Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Fluoruracila/química , Fluoruracila/farmacocinética , Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Microscopia Eletrônica , Microscopia de Fluorescência , Células NIH 3T3 , Reação em Cadeia da Polimerase Via Transcriptase Reversa , EspectrofotometriaRESUMO
Carbon dots (CDs) are novel bioimaging tools with fascinating fluorescence properties. We report here the development of novel CDs decorated on a silver-zinc oxide (CD-Ag@ZnO) nanocomposite (NC) consisting of highly fluorescent CDs and Ag@ZnO. The CD-Ag@ZnO NC was characterized by various analytical techniques. Our work provides an insight into the application of this CD-Ag@ZnO NC in monitoring cellular uptake and mediating apoptotic effects in MCF-7 and A549 cancer cell lines. By monitoring the simultaneous green fluorescence emission of the CDs, the distribution of the CD-Ag@ZnO NC could be followed, eliminating the need to use fluorescent organic dyes. Fluorescence microscopy and atomic absorption spectrometry were used for the qualitative and quantitative assessment of cellular uptake. In vitro studies of cancer cells treated with CD-Ag@ZnO NC revealed concentration-dependent cytotoxic effects via the induction of apoptosis. Fluorescence and scanning electron microscopy were used to study the characteristic nuclear and morphological changes during apoptosis. We used flow cytometry to quantify the reactive oxygen species and the reverse transcriptase polymerase chain reaction to study apoptotic gene expression. The role of reactive oxygen species in eliciting the apoptotic gene cascade was also studied. Intriguingly, the multifunctional CD-Ag@ZnO NC has a tendency to evoke apoptosis while allowing real-time intracellular trafficking, which may be of huge relevance in cancer theranostic applications.
RESUMO
Herein, we report the development of a poly(amidoamine) (PAMAM) dendrimer based multicomponent therapeutic agent for in vitro cancer therapy applications. In this approach, Generation 5 (G5) PAMAM dendrimers stabilizing silver nanoparticle surface (DsAgNPs) were used to encapsulate anticancer drug 5-fluorouracil (5-FU) to attain synergism in cancer cells. 5-FU loaded DsAg nanocomposites (5-FU@DsAgNCs) were characterized by UV-visible spectroscopy, transmission electron microscopy, X-ray diffraction, and nuclear magnetic resonance measurements. In vitro release studies certify the sustained release of 5-FU from nanocomposites. 5-FU@DsAgNCs were found to elicit a synergistic antiproliferative effect in A549 (human lung cancer) and MCF-7 (human breast cancer) cells with IC50 of 5 µg mL(-1) and 1.5 µg mL(-1), and combination index (CI) values of 0.242 and 0.178, respectively. Atomic absorption spectroscopic analyses indicated higher cellular uptake of Ag in MCF-7 than that in A549 cancer cells. Nuclear and morphological alterations, typical of apoptosis induction, were revealed by fluorescence and scanning electron microscopy imaging. An increment in reactive oxygen species (ROS) levels was measured; this indicated the induction of oxidative stress in both 5-FU@DsAgNC treated cell types. Taken together, the apoptotic effects of 5-FU@DsAgNC were more prominent in MCF-7 than in A549 cancer cells. Finally, gene expression studies suggested triggering of the p53 mediated caspase signalling gene cascade in 5-FU@DsAgNC treated cells. The strategy to use dendrimer technology to design multicomponent 5-FU@DsAgNCs is quite promising for simultaneous delivery of 5-FU and DsAgNPs to achieve synergistic anticancer effects.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/química , Sobrevivência Celular/efeitos dos fármacos , Fluoruracila/química , Nanocompostos/química , Nanopartículas/química , Poliaminas/síntese química , Poliaminas/farmacologia , Prata/química , Antineoplásicos/química , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Feminino , Fluoruracila/farmacologia , Humanos , Poliaminas/química , Difração de Raios XRESUMO
Advanced nanomaterials integrating imaging and therapeutic modalities on a single platform offers a new horizon in current cancer treatment strategies. Recently, carbon dots (CQDs) have been successfully employed for bioimaging of cancer cells. In the present study, luminescent CQDs with anionic terminus and cationic acetylated G5 poly(amido amine) (G5-Ac85) dendrimers were combined via noncovalent interactions to form self-assembled fluorescent hybrids. The fluorescence of CQDs in hybrids is enhanced in the vicinity of primary amine groups of dendrimers, making them suitable as cellular imaging probes. Encapsulation of chemo-drug epirubicin (EPI) in the dendrimer interiors endowed the fluorescent hybrids with therapeutic potential. The in vitro release of an entrapped EPI drug from CQDs@EPIâG5-Ac85 hybrids was faster in an acidic environment than under physiological conditions. Herein, multifunctional CQDs@EPIâG5-Ac85 hybrids serve as a dual-emission delivery system, to track the intracellular distribution and cytotoxic effects of EPI drugs. Green emission properties of CQDs were used for fluorescence microscopic imaging and cellular uptake by flow cytometry. Cell cycle analysis, field-emission scanning electron microscopy (FE-SEM), reactive oxygen species (ROS) generation, and up-regulation of apoptotic signaling genes unanimously demonstrated the apoptosis inducing ability of CQDs@EPIâG5-Ac85 hybrids in breast cancer (MCF-7) cells. Therefore, we have evaluated CQDs@EPIâG5-Ac85 hybrids as prospective candidates to achieve simultaneous imaging and drug delivery in cancer cells.
Assuntos
Carbono/química , Sobrevivência Celular/efeitos dos fármacos , Dendrímeros/química , Epirubicina/administração & dosagem , Microscopia de Fluorescência/métodos , Nanocápsulas/química , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/química , Difusão , Epirubicina/química , Corantes Fluorescentes/química , Humanos , Células MCF-7 , Teste de Materiais , Nanocápsulas/administração & dosagem , Nanocápsulas/ultraestrutura , Nanoconjugados/química , Nanoconjugados/ultraestrutura , Nanomedicina Teranóstica/métodosRESUMO
Currently the applications of silver nanoparticles (Ag NPs) are gaining overwhelming response due to the advancement of nanotechnology. However, only limited information is available with regard to their toxicity mechanism in different species. It is very essential to understand the complete molecular mechanism to explore the functional and long term applications of Ag NPs. Ag NPs could be toxic at cellular, subcellular, biomolecular, and epigenetic levels. Toxicity effects induced by Ag NPs have been evaluated using numerous in vitro and in vivo models, but still there are contradictions in interpretations due to disparity in methodology, test endpoints and several other model parameters which needs to be considered. Thus, this review article focuses on the progressive elucidation of molecular mechanism of toxicity induced by Ag NPs in various in vitro and in vivo models. Apart from these, this review also highlights the various ignored factors which are to be considered during toxicity studies.
Assuntos
Fenômenos Fisiológicos Celulares/efeitos dos fármacos , Dano ao DNA/fisiologia , Epigênese Genética/fisiologia , Nanopartículas Metálicas/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Prata/toxicidade , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Epigênese Genética/efeitos dos fármacos , Modelos Biológicos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologiaRESUMO
Emergence of multi-resistant organisms (MROs) leads to ineffective treatment with the currently available medications which pose a great threat to public health and food technology sectors. In this regard, there is an urgent need to strengthen the present therapies or to look over for other potential alternatives like use of "metal nanocomposites". Thus, the present study focuses on synthesis of silver-zinc oxide (Ag-ZnO) nanocomposites which will have a broad-spectrum antibacterial activity against Gram-positive and Gram-negative bacteria. Ag-ZnO nanocomposites of varied molar ratios were synthesized by simple microwave assisted reactions in the absence of surfactants. The crystalline behavior, composition and morphological analysis of the prepared powders were evaluated by X-ray diffraction, infrared spectroscopy, field emission scanning electron microscopy (FE-SEM) and atomic absorption spectrophotometry (AAS). Particle size measurements were carried out by transmission electron microscopy (TEM). Staphylococcus aureus and recombinant green fluorescent protein (GFP) expressing antibiotic resistant Escherichia coli were selected as Gram-positive and Gram-negative model systems respectively and the bactericidal activity of Ag-ZnO nanocomposite was studied. The minimum inhibitory concentration (MIC) and minimum killing concentration (MKC) of the nanocomposite against the model systems were determined by visual turbidity analysis and optical density analysis. Qualitative and quantitative assessments of its antibacterial effects were performed by fluorescent microscopy, fluorescent spectroscopy and Gram staining measurements. Changes in cellular morphology were examined by atomic force microscopy (AFM), FE-SEM and TEM. Finally, on the basis of the present investigation and previously published reports, a plausible antibacterial mechanism of Ag-ZnO nanocomposites was proposed.