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The emergence of multidrug resistance in cancer cells necessitates the development of new therapeutic modalities. One way cancer cells orchestrate energy metabolism and redox homeostasis is through overloaded iron pools directed by iron regulatory proteins, including transferrin. Here, we demonstrate that targeting redox homeostasis using nitrogen-based heterocyclic iron chelators and their iron complexes efficiently prevents the proliferation of liver cancer cells (EC50: 340 nM for IITK4003) and liver cancer 3D spheroids. These iron complexes generate highly reactive Fe(IV)=O species and accumulate lipid peroxides to promote oxidative stress in cells that impair mitochondrial function. Subsequent leakage of mitochondrial cytochrome c activates the caspase cascade to trigger the intrinsic apoptosis pathway in cancer cells. This strategy could be applied to leverage the inherent iron overload in cancer cells to selectively promote intrinsic cellular apoptosis for the development of unique iron-complex-based anticancer therapeutics.
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Extensive modifications have been made to the synthesis protocol for porous silica particles to improve the shape, size and yield percentage, but problems associated with improvement in biodegradability and decrease in chances to induce side effects still remain a concern. To circumvent these limitations, a facile modification strategy has been employed through in situ carbonization of porous silica particles. Herein, carbon particles were integrated within porous silica core-shell particles (Si-P-CNPs) during the synthesis process and found to preserve the ordered structural morphology. Curcumin was used as a model drug for loading in prepared Si-P-CNPs whereas lung cancer cells were used as a model system to study the in vitro fate. These Si-P-CNPs showed improved drug loading, drug effectivity, biodegradability and avoidance of interaction with transforming growth factor ß1 (TGF-ß1) indicating the possibility of reducing the chances of lung fibrosis and thereby enhancing the safety profile over conventional porous silica particles.
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Carbono , Curcumina , Portadores de Fármacos , Dióxido de Silicio , Factor de Crecimiento Transformador beta1 , Dióxido de Silicio/química , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/química , Humanos , Porosidad , Portadores de Fármacos/química , Carbono/química , Curcumina/química , Curcumina/farmacología , Células A549 , Línea Celular Tumoral , Fibrosis , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologíaRESUMEN
Research laboratories generate a broad range of hazardous pharmacophoric chemical contaminants, from drugs to dyes used during various experimental procedures. In the recent past, biological methods have demonstrated great potential in the remediation of such contaminants. However, the presence of pharmacophoric chemicals containing antibiotics, xenobiotics, and heavy metals suppresses the growth and survivability of used microbial agents, thus decreasing the overall efficiency of biological remediation processes. Bacterial biofilm is a natural arrangement to counter some of these inhibitions but its use in a systemic manner, portable devices, and pollutant remediation plants post serious challenges. This could be countered by synthesizing a biodegradable carbon nanoparticle from bacterial biofilm. In this study, extracellular polymeric substance-based carbon nanoparticles (Bio-EPS-CNPs) were synthesized from bacterial biofilm derived from Bacillus subtilis NCIB 3610, as a model bacterial system. The produced Bio-EPS-CNPs were investigated for physiochemical properties by dynamic light scattering, optical, Fourier-transformed infrared, and Raman spectroscopy techniques, whereas X-ray diffraction study, scanning electron microscopy, and transmission electron microscopy were used to investigate structural and morphological features. The Bio-EPS-CNPs exhibited negative surface charge with spherical morphology having a uniform size of sub-100 nm. The maximum remediation of some laboratory-produced pharmacophoric chemicals was achieved through a five-round scavenging process and confirmed by UV/Vis spectroscopic analysis with respect to the used pharmacophore. This bioinspired remediation of used pharmacophoric chemicals was achieved through the mechanism of surface adsorption via hydrogen bonding and electrostatic interactions, as revealed by different characterizations. Further experiments were performed to investigate the effects of pH, temperature, stirring, and the protocol of scavenging to establish Bio-EPS-CNP as a possible alternative to be used in research laboratories for efficient removal of pharmacophoric chemicals by incorporating it in a portable, filter-based device.
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Bacillus subtilis , Biopelículas , Carbono , Nanopartículas , Biopelículas/efectos de los fármacos , Carbono/química , Bacillus subtilis/efectos de los fármacos , Nanopartículas/química , Biodegradación Ambiental , Restauración y Remediación Ambiental/métodosRESUMEN
The improper disposal of hospital waste products containing genetic materials poses a serious safety threat. We present herein an environmentally friendly technology using a graphene-based novel carbon-allotropic surface to remediate such wastes. The used carbon-allotrope is decorated with an enediyne (EDE-1) enriched aromatic pi-conjugated structure to create an efficient and active surface for cleaving DNA strands. Under controlled exposure of ultraviolet (UV) radiation and heat, the developed surface influences genetic degradation without disturbing the bacterial populations present downstream of the water treatment system. The designed material has been extensively characterized using physicochemical and biological tools. Our results indicate that this approach can possibly be introduced in large scale hospital waste disposal streams for remediating genetic hazards and thereby developing a portable self-contained system.
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Carbono , Grafito , Bacterias , ADN , EnediinosRESUMEN
The elevated glutathione (GSH) level in cancer cells contributes to the poor response to chemotherapy and necessitates the use of maximum tolerated drug doses, leading to myriad side effects. We have developed a biocompatible and fluorescently trackable nanosystem, iron(III)-bound nanocarbonaceous polyphenol (FeNCP), to modulate the available GSH pool in cancer cells for synergistic effects in treatments with a cytotoxic anticancer drug, doxorubicin (Dox). This nanosystem was designed using a nanoscale carbon system as a platform to generate a GSH-responsive gallic acid-iron complex. The effective interaction between FeNCP and GSH was probed in PBS (pH 7.4) and cell lysates using UV-Vis, fluorescence spectrophotometry, 1H NMR, flow cytometry, and confocal and transmission electron microscopic studies. The concurrent treatment of cancer cells with subcytotoxic FeNCP and Dox leads to dose reduction indices of Dox of â¼6.1 for HepG2 (hepatocellular carcinoma) and 6.7 for B16F0 (melanoma) to kill â¼50% of the cell population, which is suggestive of the requirement of a multifold lower dose of Dox. Notably, this combination was relatively more cytotoxic toward cancer cell lines than the model normal cell line, Vero. The increased reactive oxygen species levels in combinatorial treatment reveal that FeNCP serves as a potential candidate for modulating glutathione activity and potentiating cytotoxic effects of Dox. The intelligent multifold design of this nanosystem might enable the applicability in optical detection of GSH and imaging-assisted surgery in the future, in addition to the potential to advance treatment regimens in anticancer chemotherapy.
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Antineoplásicos , Melanoma , Humanos , Hierro , Polifenoles/farmacología , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Doxorrubicina , Glutatión/metabolismo , Melanoma/tratamiento farmacológicoRESUMEN
Heart failure or myocardial infarction (MI) is one of the world's leading causes of death. Post MI, the heart can develop pathological conditions such as ischemia, inflammation, fibrosis, and left ventricular dysfunction. However, current surgical approaches are sufficient for enhancing myocardial perfusion but are unable to reverse the pathological changes. Tissue engineering and regenerative medicine approaches have shown promising effects in the repair and replacement of injured cardiomyocytes. Additionally, biomaterial scaffolds with or without stem cells are established to provide an effective environment for cardiac regeneration. Excipients loaded with growth factors, cytokines, oligonucleotides, and exosomes are found to help in such cardiac eventualities by promoting angiogenesis, cardiomyocyte proliferation, and reducing fibrosis, inflammation, and apoptosis. Injectable hydrogels, nanocarriers, cardiac patches, and vascular grafts are some excipients that can help the self-renewal in the damaged heart but are not understood well yet, in the context of used biomaterials. This review focuses on the use of various biomaterial-based approaches for the regeneration and repair of cardiac tissue postoccurrence of MI. It also discusses the outlines of cardiac remodeling and current therapeutic approaches after myocardial infarction, which are translationally important with respect to used biomaterials. It provides comprehensive details of the biomaterial-based regenerative approaches, which are currently the focus of the research for cardiac repair and regeneration and can provide a broad outline for further improvements.
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Materiales Biocompatibles , Infarto del Miocardio , Materiales Biocompatibles/uso terapéutico , Excipientes , Fibrosis , Humanos , Inflamación/tratamiento farmacológico , Infarto del Miocardio/patología , Infarto del Miocardio/terapia , RegeneraciónRESUMEN
Gastrointestinal (GI) tract is one of the hard-to-reach target tissues for the delivery of contrast agents and drugs mediated by nanoparticles due to its harsh environment. Herein, we overcame this barrier by designing orally ingestible probiotic vectors for 'hitchhiking' ultrasmall hafnia (HfO2) (â¼1-2 nm) nanoparticles. The minute-made synthesis of these nanoparticles is accomplished through a simple reduction reaction. These nanoparticles were incubated with probiotic bacteria with potential health benefits and were non-specifically taken up due to their small size. Subsequently, the bacteria were lyophilized and packed into a capsule to be administered orally as the radiopaque contrast agents for delineating the GI features. These nano-bio-hybrid entities could successfully be utilized as contrast agents in vivo in the conventional and multispectral computed tomography (CT). We demonstrated in 'color' the accumulated nanoparticles using advanced detectors of the photon counting CT. The enhanced nano-bio-interfacing capability achieved here can circumvent traditional nanoparticle solubility and delivery problems while offering a patient friendly approach for GI imaging to replace the currently practiced barium meal.
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Nanopartículas , Probióticos , Humanos , Medios de Contraste , Tracto Gastrointestinal/diagnóstico por imagen , Rayos XRESUMEN
Carbon materials are generally utilized in the form of carbon allotropes and their characteristics are exploited as such or for improving the thermal, electrical, optical, and mechanical properties of other biomaterials. This has now found a broader share in conventional biomaterial space with the generation of nanodiamond, carbon dot, carbon nanoparticles (CNPs), and so forth. With properties of better biocompatibility, intrinsic optical emission, aqueous suspendability, and easier surface conjugation possibilities made CNPs as one of the fore most choice for biological applications especially for use in intracellular spaces. There are various reports available presenting methods of preparing, characterizing, and using CNPs for various biological applications but a collection of information on what makes CNP a suitable biomaterial to achieve those biological activities is yet to be provided in a significant way. Herein, a series of correlations among synthesis, characterization, and mode of utilization of CNP have been incorporated along with the variations in its use as agent for sensing, imaging, and therapy of different diseases or conditions. It is ensembled that how simplified and optimized methods of synthesis is correlated with specific characteristics of CNPs which were found to be suitable in the specific biological applications. These comparisons and correlations among various CNPs, will surely provide a platform to generate new edition of this nanomaterial with improvised applications and newer methods of evaluating structural, physical, and functional properties. This may ensure the eventual use of CNPs for human being for specific need in near future. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > Biosensing Diagnostic Tools > In Vitro Nanoparticle-Based Sensing Therapeutic Approaches and Drug Discovery > Emerging Technologies.
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Nanopartículas , Nanoestructuras , Materiales Biocompatibles , Carbono/química , Humanos , Nanopartículas/química , NanotecnologíaRESUMEN
Effective outcome from dynamic live-cell-imaging requires utilization of a probe with high emission intensity and low photobleaching. It would be preferable to achieve such properties at a low power of the applied laser to avoid any probable damage to biological cells or tissue. Most of the used small-molecule fluorophores have been reported to show significant photobleaching in a time-dependent manner and require high laser power to gain significant intensity for bioimaging. Carbon nanoparticles have recently been successfully used for cell imaging with low bleaching characteristics but require high laser power and lack optical nonlinearity at low power levels. Here, we report the preparation, characterization, and application of a Nanoscale Carbon (NC) which, on being surface decorated with crescent-shaped poly-lysine (PLNC), provides two-photon fluorescence (TPF) and low bleaching properties. PLNC was found to stain the cytoplasm of C2C12 muscle cells in the first four-hours of incubation with high TPF in the infrared range and can be useful for deep tissue imaging with further improvements.
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Carbono , Fotones , Fluorescencia , Colorantes Fluorescentes , FotoblanqueoRESUMEN
Recent scientific findings have correlated the gut microbes with homeostasis of human health by delineating their role in pathogen resistance, bioactive metabolization, and immune responses. Foreign materials, like xenobiotics, that induce an altering effect to the human body also influence the gut microbiome to some extent and often limit their use as a result of significant side effects. Investigating the xenobiotic effect of new therapeutic material or edible could be quite painstaking and economically non-viable. Thus, the use of predictive toxicology methods can be an innovative strategy in the food, pharma, and agriculture industries. There are reported in silico, ex vivo, in vitro, and in vivo methods to evaluate such effects but with added drawbacks, such as lower predictability, physiological dissimilarities, and high cost of associated invasive procedures. This review highlights the current and future possibilities with newer modern sensing approaches of economic and time-scale advantages for predicting toxicological responses on gut microbiomes.
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Microbioma Gastrointestinal , Microbiota , Simulación por Computador , Alimentos , Humanos , Xenobióticos/toxicidadRESUMEN
A new pH-responsive cationic co-liposomal formulation was prepared in this study using the twin version of the amphiphile palmitoyl homocysteine, TPHC; natural zwitterionic lipid, DOPE; and cholesterol-based twin cationic lipid, C5C, at specified molar ratios. This co-liposome was further decorated with a newly designed fluorescently tagged, cholesterol-tethered EpCAM-targeting RNA aptamer for targeted gene delivery. This aptamer-guided nanoliposomal formulation, C5C/DOPE/TPHC at 8:24:1 molar ratio, could efficiently transport the genes in response to low pH of cellular endosomes selectively to the EpCAM overexpressing cancer stem cells. This particular observation was extended using siRNA against GFP to validate their transfection capabilities in response to EpCAM expression. Overall, the aptamer-guided nanoliposomal formulation was found to be an excellent transfectant for in vitro siRNA gene delivery.
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Neoplasias , Técnicas de Transferencia de Gen , Humanos , Concentración de Iones de Hidrógeno , Neoplasias/tratamiento farmacológico , Células Madre Neoplásicas , TransfecciónRESUMEN
Metal-organic frameworks (MOFs) have applications in numerous fields. However, the development of MOF-based "theranostic" macroscale devices is not achieved. Here, heparin-coated biocompatible MOF/poly(ε-caprolactone) (PCL) "theranostic" stents are developed, where NH2 -Materials of Institute Lavoisier (MIL)-101(Fe) encapsulates and releases rapamycin (an immunosuppressive drug). These stents also act as a remarkable source of contrast in ex vivo magnetic resonance imaging (MRI) compared to the invisible polymeric stent. The in vitro release patterns of heparin and rapamycin respectively can ensure a type of programmed model to prevent blood coagulation immediately after stent placement in the artery and stenosis over a longer term. Due to the presence of hydrolysable functionalities in MOFs, the stents are shown to be highly biodegradable in degradation tests under various conditions. Furthermore, there is no compromise of mechanical strength or flexibility with MOF compositing. The system described here promises many biomedical applications in macroscale theranostic devices. The use of MOF@PCL can render a medical device MRI-visible while simultaneously acting as a carrier for therapeutic agents.
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Stents Liberadores de Fármacos , Estructuras Metalorgánicas , Imagen por Resonancia Magnética , Estructuras Metalorgánicas/farmacología , Sirolimus/farmacología , StentsRESUMEN
By using complementary DNA sequences as surface ligands, we selectively allow two individual diffusing "dual-color" carbon dots to interact in situ and in vitro. Spontaneous nanoscale oxidation of surface-abundant nitroso-/nitro-functionalities leads to two distinctly colored carbon dots (CD) which are isolated by polarity driven chromatographic separation. Green- and red-emitting carbon dots (gCD and rCD) were decorated by complementary single-stranded DNAs which produce a marked increase in the fluorescence emission of the respective carbon dots. Mutual colloidal interactions are achieved through hybridization of complementary DNA base pairs attached to the respective particles, resulting in quenching of their photoluminescence. The observed post-hybridization quenching is presumably due to a combined effect from an aggregation of CDs post duplex DNA formation and close proximity of multicolored CDs, having overlapped spectral regions leading to a nonradiative energy transfer process possibly released as heat. This strategy may contribute to the rational design of mutually interacting carbon dots for a better control over the resulting assembly structure for studying different biological phenomenon including molecular cytogenetics. One of the newly synthesized CDs was successfully used to image intracellular location of GAPDH mRNA using an event of change in fluorescence intensity (FI) of CDs. This selectivity was introduced by conjugating an oligonucleotide harboring complementary sequence to GAPDH mRNA. FI of this conjugated carbon dot, rCD-GAPDH, was also found to decrease in the presence of Ca2+, varied in relation to H+ concentrations, and could serve as a tool to quantify the intracellular concentrations of Ca2+ and pH value (H+) which can give important information about cell survival. Therefore, CD-oligonucleotide conjugates could serve as efficient probes for cellular events and interventions.
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Técnicas Biosensibles , Gliceraldehído-3-Fosfato Deshidrogenasa (Fosforilante)/aislamiento & purificación , Hibridación de Ácido Nucleico , Oligonucleótidos/química , Carbono/química , ADN de Cadena Simple/química , Gliceraldehído-3-Fosfato Deshidrogenasa (Fosforilante)/química , Humanos , Puntos Cuánticos/química , ARN Mensajero/química , ARN Mensajero/aislamiento & purificaciónRESUMEN
Ocular drug delivery has always been a challenging feat to achieve in the field of medical sciences. One of the existing methods of non-invasive ocular drug delivery is the use of eye drops. However, drugs administered through these formulations have low bioavailability in the ocular system. This limitation can been overcome by using contact lenses as drug delivery vehicles. According to USA FDA definitions they can be categorized into two main categories-hard and soft contact lenses. Based on the material properties, hard contact lenses are mostly produced from polymers of acrylate monomers such as MMA (methyl methacrylate). These have the least water retention capacity, thereby, having minimal ability to diffuse oxygen into the corneal layer and are not ideal for long term use. Soft material contact lenses are flexible and are mainly hydrogel based. They have higher water retention capacities as compared to rigid contact lenses, which gives them the ability to transmit oxygen to the corneal layer. These hydrogel based soft materials are mainly produced from polymers of acrylate monomers such as HEMA (hydroxyethyl methacrylate) and found to be better for drug delivery contact lenses. These polymer-based soft materials have been efficiently modified in terms of their chemistry to achieve diverse physicochemical properties to produce efficient ocular drug delivery systems. However, complications such as drug leaching during storage and distribution, sterilisation, preservation of integrity of the lens and the possibility of surface roughness due to the incorporated drug molecules still need to be optimised. This review highlights the chemistries of various polymeric molecules through which physicochemical properties can be modified to achieve optimum drug loading and sustained release of the drug for application in the ocular system.
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A liposomal formulation comprising a dicationic cholesterol based lipid, Chol+-(CH2)5-Chol+, and a helper zwitterionic lipid, DOPE (1:4), was prepared to deliver polynucleotides of different topologies, molecular weights, and backbones. This formulation was used to transfect HeLa cells with circular and linearized plasmid pEGFP-C3. The transfection efficiency of the dicationic cholesterol based coliposomal formulation Chol+-(CH2)5-Chol+/DOPE (1:4) was observed to be better when compared against different commercial delivery agents, Lipofectamine2000, Effectene, and a known oligonucleotide delivery agent, Oligofectamine. The efficacy was also compared with the respective monocationic cholesterol based liposomal formulations. Western blot analysis for Smad2 protein detection showed almost 100% downregulation of the Smad2 protein by polynucleotides delivered by Chol+-(CH2)5-Chol+/DOPE (1:4), which was better than that with Oligofectamine and Effectene. Similarly, semiquantitative RT-PCR showed the downregulation of Smad2 RNA along with that of a downstream target of Smad2, Id2. The higher efficiency of different types of nucleic acid delivery was also evident with Chol+-(CH2)5-Chol+/DOPE (1:4) in A549 cells. As an added benefit, the formulation Chol+-(CH2)5-Chol+/DOPE (1:4) was found to be highly biocompatible at all the compositions investigated herein.
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Photoacoustic imaging has emerged as a promising imaging platform with a high tissue penetration depth. However, biodegradable nanoparticles, especially those for photoacoustic imaging, are rare and limited to a few polymeric agents. The development of such nanoparticles holds great promise for clinically translatable diagnostic imaging with high biocompatibility. Metabolically digestible and inherently photoacoustic imaging probes can be developed from nanoprecipitation of biliverdin, a naturally occurring heme-based pigment. The synthesis of nanoparticles composed of a biliverdin network, cross-linked with a bifunctional amine linker, is achieved where spectral tuning relies on the choice of reaction media. Nanoparticles synthesized in water or water containing sodium chloride exhibit higher absorbance and lower fluorescence compared to nanoparticles synthesized in 2-(N-morpholino)ethanesulfonic acid buffer. All nanoparticles display high absorbance at 365 and 680 nm. Excitation at near-infrared wavelengths leads to a strong photoacoustic signal, while excitation with ultraviolet wavelengths results in fluorescence emission. In vivo photoacoustic imaging experiments in mice demonstrated that the nanoparticles accumulate in lymph nodes, highlighting their potential utility as photoacoustic agents for sentinel lymph node detection. The biotransformation of these agents was studied using mass spectroscopy, and they were found to be completely biodegraded in the presence of biliverdin reductase, a ubiquitous enzyme found in the body. Degradation of these particles was also confirmed in vivo. Thus, the nanoparticles developed here are a promising platform for biocompatible biological imaging due to their inherent photoacoustic and fluorescent properties as well as their complete metabolic digestion.
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Biliverdina/química , Ganglios Linfáticos/diagnóstico por imagen , Nanopartículas/química , Imagen Óptica , Técnicas Fotoacústicas , Animales , Biliverdina/síntesis química , Biliverdina/metabolismo , Línea Celular Tumoral , Supervivencia Celular , Humanos , Hidrodinámica , Células MCF-7 , Ratones , Ratones Desnudos , Nanopartículas/metabolismo , Tamaño de la Partícula , Propiedades de Superficie , PorcinosRESUMEN
Transcription factor STAT3 has been shown to regulate genes that are involved in stem cell self-renewal and thus represents a novel therapeutic target of great biological significance. However, many small-molecule agents with potential effects through STAT3 modulation in cancer therapy lack aqueous solubility and high off-target toxicity, hence impeding efficient bioavailability and activity. This work, for the first time, reports a prodrug-based strategy for selective and safer delivery of STAT3 inhibitors designed toward metastatic and drug-resistant breast cancer. We have synthesized a novel lipase-labile SN-2 phospholipid prodrug from a clinically investigated STAT3 inhibitor, nifuroxazide (Pro-nifuroxazide), which can be regioselectively cleaved by the membrane-abundant enzymes in cancer cells. Pro-nifuroxazide self-assembled to sub 20 nm nanoparticles (NPs), and the cytotoxic ability was screened in ER(+)-MCF-7 and ER(-)-MD-MB231 cells at 48-72 h using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra-zolium bromide proliferation assay. Results indicated that Pro-nifuroxazide NPs are multifold more effective toward inhibiting cancer cells in a time-dependent manner compared to parent nifuroxazide. A remarkable improvement in the local concentration of drugs to as high as â¼240 fold when assembled into NPs is presumably the reason for this functional improvement. We also introduced molecular dynamics simulations to generate Pro-nifuroxazide nano-assembly, as a model assembly from triggerable anti-cancer drugs, to provide molecular insights correlating physicochemical and anti-cancer properties. In silico properties of Pro-nifuroxazide including size, chemistry of NPs and membrane interactions with individual molecules could be validated by in vitro functional activities in cells of breast cancer origin. The in vivo anti-cancer efficiencies of Pro-nifuroxazide NPs in nude mice xenografts with MCF-7 revealed remarkable growth inhibition of as high as 400%. Histopathological analysis corroborated these findings to show significantly high nuclear fragmentation and retracted cytoplasm. Immunostaining on tumor section demonstrated a significantly lower level of pSTAT-3 by Pro-nifuroxazide NP treatment, establishing the inhibition of STAT-3 phosphorylation. Our strategy for the first time proposes a translatable prodrug agent self-assembled into NPs and demonstrates remarkable enhancement in IC50, induced apoptosis, and reduced cancer cell population through STAT-3 inhibition via reduced phosphorylation.
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Antineoplásicos , Hidroxibenzoatos , Nanomedicina , Neoplasias , Nitrofuranos , Profármacos , Animales , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Humanos , Hidroxibenzoatos/química , Hidroxibenzoatos/farmacocinética , Hidroxibenzoatos/farmacología , Células MCF-7 , Ratones , Ratones Desnudos , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/patología , Nitrofuranos/química , Nitrofuranos/farmacocinética , Nitrofuranos/farmacología , Profármacos/química , Profármacos/farmacocinética , Profármacos/farmacología , Factor de Transcripción STAT3/antagonistas & inhibidores , Factor de Transcripción STAT3/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
In this work, an ultra-sensitive electrochemical-digital sensor chip is devised for potential use as a digital stress analyzer for point-of-care testing (POCT) and preventive on-site recording of the hormone 'cortisol', a glucocorticoid class of steroid hormone present in the human saliva. The sensor was interfaced and re-configured with a high precision impedance converter system (AD5933) and used for electrochemical impedance spectroscopy (EIS) to evaluate the cortisol levels in seven saliva samples. To obtain enhanced biological (cortisol) recognition and achieve a lower limit of detection 0.87 ± 0.12 pg mL-1 (2.4 ± 0.38 pmol mL-1) with a wide range from 1 pg mL-1 to 10 ng mL-1 (2.75 pmol mL-1 to 27.58 pmol mL-1; R2 = 0.9831), bovine serum albumin (1% BSA) was utilized as an effective sensitivity enhancer in addition to optimizing the other two parameters: (i) anti-cortisol antibody (anti-CAb) covalently attached to micro-Au electrodes and (ii) saliva sample incubation time on the sensor chip. The results obtained in this work were corroborated with the gold standard ELISA test with an accuracy of 96.3% and other previously reported biosensors. We envisage that the conceivable standpoint of this study can be a practice towards new development in cortisol biosensing, which will be pertinent to POCT targeted for in vitro psychobiological study on patient cortisol in saliva, and finally an implantable sensor chip in the future.
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Técnicas Biosensibles/métodos , Glucocorticoides/análisis , Inmunoensayo/métodos , Límite de Detección , Saliva/química , Electroquímica , Humanos , Hidrocortisona/análisisRESUMEN
Manipulating the chiroptical properties at the nanoscale is of great importance in stereoselective reactions, enantioseparation, self-assembly, and biological phenomena. In recent years, carbon dots have garnered great attention because of their favorable properties such as tunable fluorescence, high biocompatibility, and facile, scalable synthetic procedures. Herein, we report for the first time the unusual behavior of cyclic amino acids on the surface of carbon dots prepared via microwave-based carbonization. Various amino acids were introduced on the surface of carbon dots via EDC/NHS conjugation at room temperature. Circular dichroism results revealed that although most of the surface conjugated amino acids can preserve their chirality on negatively charged, "bare" carbon dots, the "handedness" of cyclic α-amino acids can be flipped when covalently attached on carbon dots. Moreover, these chiroptical carbon dots were found to interact with the cellular membrane or its mimic in a highly selective manner due to their acquired asymmetric selectivity. A comprehensive inhibitor study was conducted to investigate the pathway of cellular trafficking of these carbon dots. Overall, it was concluded that the chirality of the amino acid on the surface of carbon dots could regulate many of the cellular processes.