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1.
Redox Biol ; 72: 103144, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38613920

RESUMO

Nitric oxide (NO) is a key signalling molecule released by vascular endothelial cells that is essential for vascular health. Low NO bioactivity is associated with cardiovascular diseases, such as hypertension, atherosclerosis, and heart failure and NO donors are a mainstay of drug treatment. However, many NO donors are associated with the development of tolerance and adverse effects, so new formulations for controlled and targeted release of NO would be advantageous. Herein, we describe the design and characterisation of a novel NO delivery system via the reaction of acidified sodium nitrite with thiol groups that had been introduced by cysteamine conjugation to porous graphene oxide nanosheets, thereby generating S-nitrosated nanosheets. An NO electrode, ozone-based chemiluminescence and electron paramagnetic resonance spectroscopy were used to measure NO released from various graphene formulations, which was sustained at >5 × 10-10 mol cm-2 min-1 for at least 3 h, compared with healthy endothelium (cf. 0.5-4 × 10-10 mol cm-2 min-1). Single cell Raman micro-spectroscopy showed that vascular endothelial and smooth muscle cells (SMCs) took up graphene nanostructures, with intracellular NO release detected via a fluorescent NO-specific probe. Functionalised graphene had a dose-dependent effect to promote proliferation in endothelial cells and to inhibit growth in SMCs, which was associated with cGMP release indicating intracellular activation of canonical NO signalling. Chemiluminescence detected negligible production of toxic N-nitrosamines. Our findings demonstrate the utility of porous graphene oxide as a NO delivery vehicle to release physiologically relevant amounts of NO in vitro, thereby highlighting the potential of these formulations as a strategy for the treatment of cardiovascular diseases.


Assuntos
Grafite , Óxido Nítrico , Grafite/química , Óxido Nítrico/metabolismo , Humanos , Nanoestruturas/química , Porosidade , Doadores de Óxido Nítrico/química , Doadores de Óxido Nítrico/farmacologia , Doadores de Óxido Nítrico/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Doenças Cardiovasculares/tratamento farmacológico , Células Endoteliais/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos
2.
Nitric Oxide ; 147: 42-50, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38631610

RESUMO

Nitric oxide (NO) donating drugs such as organic nitrates have been used to treat cardiovascular diseases for more than a century. These donors primarily produce NO systemically. It is however sometimes desirable to control the amount, location, and time of NO delivery. We present the design of a novel pH-sensitive NO release system that is achieved by the synthesis of dipeptide diphenylalanine (FF) and graphene oxide (GO) co-assembled hybrid nanosheets (termed as FF@GO) through weak molecular interactions. These hybrid nanosheets were characterised by using X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, zeta potential measurements, X-ray photoelectron spectroscopy, scanning and transmission electron microscopies. The weak molecular interactions, which include electrostatic, hydrogen bonding and π-π stacking, are pH sensitive due to the presence of carboxylic acid and amine functionalities on GO and the dipeptide building blocks. Herein, we demonstrate that this formulation can be loaded with NO gas with the dipeptide acting as an arresting agent to inhibit NO burst release at neutral pH; however, at acidic pH it is capable of releasing NO at the rate of up to 0.6 µM per minute, comparable to the amount of NO produced by healthy endothelium. In conclusion, the innovative conjugation of dipeptide with graphene can store and release NO gas under physiologically relevant concentrations in a pH-responsive manner. pH responsive NO-releasing organic-inorganic nanohybrids may prove useful for the treatment of cardiovascular diseases and other pathologies.


Assuntos
Grafite , Nanoestruturas , Óxido Nítrico , Grafite/química , Concentração de Íons de Hidrogênio , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Nanoestruturas/química , Humanos , Dipeptídeos/química , Fenilalanina/química , Fenilalanina/análogos & derivados
3.
ACS Biomater Sci Eng ; 10(4): 1946-1965, 2024 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-38427627

RESUMO

Various nanomaterials have recently become fascinating tools in cancer diagnostic applications because of their multifunctional and inherent molecular characteristics that support efficient diagnosis and image-guided therapy. Zein nanoparticles are a protein derived from maize. It belongs to the class of prolamins possessing a spherical structure with conformational properties similar to those of conventional globular proteins like ribonuclease and insulin. Zein nanoparticles have gained massive interest over the past couple of years owing to their natural hydrophilicity, ease of functionalization, biodegradability, and biocompatibility, thereby improving oral bioavailability, nanoparticle targeting, and prolonged drug administration. Thus, zein nanoparticles are becoming a promising candidate for precision cancer drug delivery. This review highlights the clinical significance of applying zein nanosystems for cancer theragnostic─moreover, the role of zein nanosystems for cancer drug delivery, anticancer agents, and gene therapy. Finally, the difficulties and potential uses of these NPs in cancer treatment and detection are discussed. This review will pave the way for researchers to develop theranostic strategies for precision medicine utilizing zein nanosystems.


Assuntos
Antineoplásicos , Neoplasias , Zeína , Humanos , Portadores de Fármacos/uso terapêutico , Zeína/química , Sistemas de Liberação de Medicamentos , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Antineoplásicos/uso terapêutico
4.
Nanomedicine (Lond) ; 18(28): 2101-2104, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38059500

RESUMO

Tweetable abstract Mitochondria are increasingly a target for drug delivery in cardiovascular diseases. This editorial describes how a nanomedicine approach may improve drug potency and efficacy in a safe and controlled manner.


Assuntos
Nanomedicina , Nanopartículas , Sistemas de Liberação de Medicamentos , Coração , Mitocôndrias
5.
ACS Omega ; 8(32): 29674-29684, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37599955

RESUMO

Graphene oxide (GO) is a conventional yet vital precursor for the synthesis of porous graphene (PG). Several strong oxidizing agents such as potassium permanganate and perchlorates are typically used for oxidization of graphite. However, they expose toxic reactants/products that harm the environment. Therefore, a greener approach is desperately needed to oxidize and exfoliate graphite. This study reports for the first time on successful oxidation of graphite by ferrate(VI) compounds via an encapsulation approach. By further reducing GO prepared from this near green route with vitamin C, PG anticipated by many highly important and expanding areas such as water treatment could be readily achieved. X-ray diffraction (XRD), Fourier transform infrared (FTIR) and UV-vis spectroscopy, and scanning electronic microscopy (SEM) along with energy-dispersive spectroscopy confirmed the high yield of GO from the oxidation of graphite. Raman spectroscopy, XRD, and TEM confirmed the formation of high-quality few-layered PG from the reduction of as-prepared GO. The above results demonstrated the practicality of using encapsulated ferrate(VI) compounds to realize green oxidation of graphite and resolve the paradox about the oxidation capability of ferrate(VI). To further illustrate its potential for the removal of emerging and crucial contaminants from water, as-prepared PG was further examined against the contaminants of methyl orange (MeO) dye and ibuprofen (IBU). Taken together, the results revealed that more than 90% removal efficiency could be achieved at a high PG dosage against MeO and IBU. This ground-breaking greener approach opens the door to risk-free, extensive graphene environmental applications.

6.
APL Bioeng ; 7(3): 031502, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37614868

RESUMO

The rapid development of powerful anti-oncology medicines have been possible because of advances in nanomedicine. Photothermal therapy (PTT) is a type of treatment wherein nanomaterials absorb the laser energy and convert it into localized heat, thereby causing apoptosis and tumor eradication. PTT is more precise, less hazardous, and easy-to-control in comparison to other interventions such as chemotherapy, photodynamic therapy, and radiation therapy. Over the past decade, various nanomaterials for PTT applications have been reviewed; however, a comprehensive study of graphene quantum dots (GQDs) has been scantly reported. GQDs have received huge attention in healthcare technologies owing to their various excellent properties, such as high water solubility, chemical stability, good biocompatibility, and low toxicity. Motivated by the fascinating scientific discoveries and promising contributions of GQDs to the field of biomedicine, we present a comprehensive overview of recent progress in GQDs for PTT. This review summarizes the properties and synthesis strategies of GQDs including top-down and bottom-up approaches followed by their applications in PTT (alone and in combination with other treatment modalities such as chemotherapy, photodynamic therapy, immunotherapy, and radiotherapy). Furthermore, we also focus on the systematic study of in vitro and in vivo toxicities of GQDs triggered by PTT. Moreover, an overview of PTT along with the synergetic application used with GQDs for tumor eradication are discussed in detail. Finally, directions, possibilities, and limitations are described to encourage more research, which will lead to new treatments and better health care and bring people closer to the peak of human well-being.

7.
Drug Discov Today ; 28(9): 103673, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37331691

RESUMO

Chronic wounds are ubiquitously inhabited by bacteria, and they remain a challenge as they cause significant discomfort and because their treatment consumes huge clinical resources. To reduce the burden that chronic wounds place upon both patients and health services, a wide variety of approaches have been devised and investigated. Bioinspired nanomaterials have shown great success in wound healing when compared to existing approaches, showing better ability to mimic natural extracellular matrix (ECM) components and thus to promote cell adhesion, proliferation, and differentiation. Wound dressings that are based on bioinspired nanomaterials can be engineered to promote anti-inflammatory mechanisms and to inhibit the formation of microbial biofilms. We consider the extensive potential of bioinspired nanomaterials in wound healing, revealing a scope beyond that covered previously.


Assuntos
Anti-Infecciosos , Nanoestruturas , Humanos , Cicatrização , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico
8.
Int J Biol Macromol ; 242(Pt 1): 124741, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37156311

RESUMO

Salmonella Typhi is an intracellular bacterium causing a variety of enteric diseases, being typhoid fever the most common. Current modalities for treating S. typhi infection are subjected to multi-drug resistance. Herein, a novel macrophage targeting approach was developed via coating bioinspired mannosylated preactivated hyaluronic acid (Man-PTHA) ligands on a self-nanoemulsifying drug delivery system (SNEDDS) loaded with the anti-bacterial drug ciprofloxacin (CIP). The shake flask method was used to determine the drug solubility in the different excipients (oil, surfactants and co-surfactants). Man-PTHA were characterized by physicochemical, in vitro, and in vivo parameters. The mean droplet size was 257 nm, with a PDI of 0.37 and zeta potential of -15 mV. In 72 h, 85 % of the drug was released in a sustained manner, and the entrapment efficiency was 95 %. Outstanding biocompatibility, mucoadhesion, muco-penetration, anti-bacterial action and hemocompatibility were observed. Intra-macrophage survival of S. typhi was minimal (1 %) with maximum nanoparticle uptake, as shown by their higher fluorescence intensity. Serum biochemistry evaluation showed no significant changes or toxicity, and histopathological evaluation confirmed the entero-protective nature of the bioinspired polymers. Overall, results confirm that Man-PTHA SNEDDS can be employed as novel and effective delivery systems for the therapeutic management of S. typhi infection.


Assuntos
Infecções Bacterianas , Nanopartículas , Nanoestruturas , Humanos , Masculino , Ácido Hialurônico , Emulsões/química , Sistemas de Liberação de Medicamentos/métodos , Nanoestruturas/química , Tensoativos/química , Solubilidade , Nanopartículas/química , Tamanho da Partícula , Administração Oral
9.
Biochim Biophys Acta Mol Basis Dis ; 1869(6): 166746, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37160171

RESUMO

Cellular and stromal components including tumor cells, immune cells, mesenchymal cells, cancer-linked fibroblasts, and extracellular matrix, constituent tumor microenvironment (TME). TME plays a crucial role in reprogramming tumor initiation, uncontrolled proliferation, invasion and metastasis as well as response to therapeutic modalities. In recent years targeting the TME has developed as a potential strategy for treatment of cancer because of its life-threatening functions in restricting tumor development and modulating responses to standard-of-care medicines. Cold atmospheric plasma, oncolytic viral therapy, bacterial therapy, nano-vaccine, and repurposed pharmaceuticals with combination therapy, antiangiogenic drugs, and immunotherapies are among the most effective therapies directed by TME that have either been clinically authorized or are currently being studied. This article discusses above-mentioned therapies in light of targeting TME. We also cover problems related to the TME-targeted therapies, as well as future insights and practical uses in this rapidly growing field.


Assuntos
Neoplasias , Humanos , Neoplasias/patologia , Imunoterapia , Fibroblastos/patologia , Microambiente Tumoral
10.
Drug Discov Today ; 28(6): 103577, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37004983

RESUMO

In recent years, immunotherapy for cancer treatment using monoclonal antibodies has shown clinical success, particularly with programmed cell death protein 1 (PD-1) and its ligand programmed death-ligand 1 (PD-L1). Dostarlimab, an immune checkpoint inhibitor, interacts with adaptive immunity by binding to human PD-1, inhibiting PD-L1 and PD-L2 interactions, and cross-talk with adaptive immunity. Recent clinical trials have shown that dostarlimab is effective in treating mismatch repair deficiency (dMMR) in endometrial cancer patients, leading to its approval in the United States and the European Union in 2021. This article provides a comprehensive overview of dostarlimab, its therapeutic ability, and the different indications for which it is being used. Dostarlimab could serve as a potential alternative to many cancer treatments that frequently have severe consequences on patients' quality of life.


Assuntos
Neoplasias Colorretais , Receptor de Morte Celular Programada 1 , Humanos , Antígeno B7-H1 , Qualidade de Vida
11.
Biomaterials ; 296: 122075, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36931103

RESUMO

Skin-interfaced electronics (skintronics) have received considerable attention due to their thinness, skin-like mechanical softness, excellent conformability, and multifunctional integration. Current advancements in skintronics have enabled health monitoring and digital medicine. Particularly, skintronics offer a personalized platform for early-stage disease diagnosis and treatment. In this comprehensive review, we discuss (1) the state-of-the-art skintronic devices, (2) material selections and platform considerations of future skintronics toward intelligent healthcare, (3) device fabrication and system integrations of skintronics, (4) an overview of the skintronic platform for personalized healthcare applications, including biosensing as well as wound healing, sleep monitoring, the assessment of SARS-CoV-2, and the augmented reality-/virtual reality-enhanced human-machine interfaces, and (5) current challenges and future opportunities of skintronics and their potentials in clinical translation and commercialization. The field of skintronics will not only minimize physical and physiological mismatches with the skin but also shift the paradigm in intelligent and personalized healthcare and offer unprecedented promise to revolutionize conventional medical practices.


Assuntos
COVID-19 , Dispositivos Eletrônicos Vestíveis , Humanos , SARS-CoV-2 , Eletrônica , Atenção à Saúde
12.
Adv Healthc Mater ; 12(17): e2203148, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36802199

RESUMO

Gelatin is a widely utilized bioprinting biomaterial due to its cell-adhesive and enzymatically cleavable properties, which improve cell adhesion and growth. Gelatin is often covalently cross-linked to stabilize bioprinted structures, yet the covalently cross-linked matrix is unable to recapitulate the dynamic microenvironment of the natural extracellular matrix (ECM), thereby limiting the functions of bioprinted cells. To some extent, a double network bioink can provide a more ECM-mimetic, bioprinted niche for cell growth. More recently, gelatin matrices are being designed using reversible cross-linking methods that can emulate the dynamic mechanical properties of the ECM. This review analyzes the progress in developing gelatin bioink formulations for 3D cell culture, and critically analyzes the bioprinting and cross-linking techniques, with a focus on strategies to optimize the functions of bioprinted cells. This review discusses new cross-linking chemistries that recapitulate the viscoelastic, stress-relaxing microenvironment of the ECM, and enable advanced cell functions, yet are less explored in engineering the gelatin bioink. Finally, this work presents the perspective on the areas of future research and argues that the next generation of gelatin bioinks should be designed by considering cell-matrix interactions, and bioprinted constructs should be validated against currently established 3D cell culture standards to achieve improved therapeutic outcomes.


Assuntos
Bioimpressão , Alicerces Teciduais , Alicerces Teciduais/química , Engenharia Tecidual/métodos , Gelatina/química , Impressão Tridimensional , Materiais Biocompatíveis/química , Bioimpressão/métodos , Hidrogéis/química
13.
Adv Healthc Mater ; 12(6): e2201523, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36511355

RESUMO

Over the past decade, there have been many interesting studies in the scientific literature about the interaction of graphene-based polymeric nanocomposites with microorganisms to tackle antimicrobial resistance. These studies have reported variable intensities of biocompatibility and selectivity for the nanocomposites toward a specific strain, but it is widely believed that graphene nanocomposites have antibacterial, antiviral, and antifungal activities. Such antibacterial activity is due to several mechanisms by which graphene nanocomposites can act on cells including stimulating oxidative stress; disrupting membranes due to sharp edges; greatly changing core structure mechanical strength and coarseness. However, the underlying mechanisms of graphene nanocomposites as antiviral and antifungal agents remain relatively scarce. In this review, recent advances in the synthesis, functional tailoring, and antibacterial, antiviral, and antifungal applications of graphene nanocomposites are summarized. The synthesis of graphene materials and graphene-based polymeric nanocomposites with techniques such as pressurized gyration, electrospinning, chemical vapor deposition, and layer-by-layer self-assembly is first introduced. Then, the antimicrobial mechanisms of graphene membranes are presented and demonstrated typical in vitro and in vivo studies on the use of graphene nanocomposites for antibacterial, antiviral, and antifungal applications. Finally, the review describes the biosafety, current limitations, and potential of antimicrobial graphene-based nanocomposites.


Assuntos
Grafite , Nanocompostos , Antifúngicos/farmacologia , Grafite/farmacologia , Grafite/química , Antivirais/farmacologia , Nanocompostos/química , Antibacterianos/farmacologia , Antibacterianos/química , Polímeros/química
14.
Appl Phys Rev ; 10: 041310, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38229764

RESUMO

Nitric oxide (NO) signaling plays many pivotal roles impacting almost every organ function in mammalian physiology, most notably in cardiovascular homeostasis, inflammation, and neurological regulation. Consequently, the ability to make real-time and continuous measurements of NO is a prerequisite research tool to understand fundamental biology in health and disease. Despite considerable success in the electrochemical sensing of NO, challenges remain to optimize rapid and highly sensitive detection, without interference from other species, in both cultured cells and in vivo. Achieving these goals depends on the choice of electrode material and the electrode surface modification, with graphene nanostructures recently reported to enhance the electrocatalytic detection of NO. Due to its single-atom thickness, high specific surface area, and highest electron mobility, graphene holds promise for electrochemical sensing of NO with unprecedented sensitivity and specificity even at sub-nanomolar concentrations. The non-covalent functionalization of graphene through supermolecular interactions, including π-π stacking and electrostatic interaction, facilitates the successful immobilization of other high electrolytic materials and heme biomolecules on graphene while maintaining the structural integrity and morphology of graphene sheets. Such nanocomposites have been optimized for the highly sensitive and specific detection of NO under physiologically relevant conditions. In this review, we examine the building blocks of these graphene-based electrochemical sensors, including the conjugation of different electrolytic materials and biomolecules on graphene, and sensing mechanisms, by reflecting on the recent developments in materials and engineering for real-time detection of NO in biological systems.

15.
Front Med (Lausanne) ; 9: 1032899, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36507513

RESUMO

As the world has experienced in the Coronavirus Disease 2019 pandemic, viral infections have devastating effects on public health. Personal protective equipment with high antiviral features has become popular among healthcare staff, researchers, immunocompromised people and more to minimize this effect. Graphene and its derivatives have been included in many antimicrobial studies due to their exceptional physicochemical properties. However, scientific studies on antiviral graphene are much more limited than antibacterial and antifungal studies. The aim of this study was to produce nanocomposite fibers with high antiviral properties that can be used for personal protective equipment and biomedical devices. In this work, 10 wt% polycaprolactone-based fibers were prepared with different concentrations (0.1, 0.5, 1, 2, 4 w/w%) of porous graphene, graphene oxide and graphene foam in acetone by using electrospinning. SEM, FTIR and XRD characterizations were applied to understand the structure of fibers and the presence of materials. According to SEM results, the mean diameters of the porous graphene, graphene oxide and graphene foam nanofibers formed were around 390, 470, and 520 nm, respectively. FTIR and XRD characterization results for 2 w/w% concentration nanofibers demonstrated the presence of graphene oxide, porous graphene and graphene foam nanomaterials in the fiber. The antiviral properties of the formed fibers were tested against Pseudomonas phage Phi6. According to the results, concentration-dependent antiviral activity was observed, and the strongest viral inhibition graphene oxide-loaded nanofibers were 33.08 ± 1.21% at the end of 24 h.

16.
Pharmaceutics ; 14(11)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36365165

RESUMO

The present study is aimed to develop and optimize levosulpiride-loaded nanostructured lipid carriers (LSP-NLCs) for improving oral bioavailability and prokinetic activity of LSP. LSP-NLCs were optimized with D-optimal mixture design using solid lipid, liquid lipid and surfactant concentrations as independent variables. The prepared LSP-NLCs were evaluated for physicochemical properties and solid-state characterization. The in vivo oral pharmacokinetics and prokinetic activity of LSP-NLCs were evaluated in rats. LSP-NLCs formulation was optimized at Precirol® ATO 5/Labrasol (80.55/19.45%, w/w) and Tween 80/Span 80 concentration of 5% (w/w) as a surfactant mixture. LSP-NLCs showed a spherical shape with a particle size of 152 nm, a polydispersity index of 0.230 and an entrapment efficiency of 88%. The DSC and PXRD analysis revealed conversion of crystalline LSP to amorphous state after loading into the lipid matrix. LSP-NLCs displayed a 3.42- and 4.38-flods increase in AUC and Cmax after oral administration compared to LSP dispersion. In addition, LSP-NLCs showed enhanced gastric emptying (61.4%), intestinal transit (63.0%), and fecal count (68.8) compared to LSP dispersion (39.7%, 38.0% and 51.0, respectively). Taken together, these results show improved oral bioavailability and prokinetic activity of LSP-NLCs and presents a promising strategy to improve therapeutic activity of LSP for efficient treatment of gastric diseases.

17.
Pharmaceutics ; 14(11)2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36365252

RESUMO

The enteric system residing notorious Salmonella typhimurium (S. typhi) is an intracellular, food-borne, and zoonotic pathogen causing typhoid fever. Typhoid fever is one of the leading causes of mortality and morbidity in developing and underdeveloped countries. It also increased the prevalence of multidrug resistance globally. Currently, available anti-bacterial modalities are unable to penetrate into the intracellular compartments effectively for eradicating S. typhi infection. Therefore, in this study, we developed nanostructured lipid-based carriers in the form of a self-nanoemulsifying drug delivery system (SNEDDS) for targeted delivery of ciprofloxacin (CIP) into the S. typhi intracellular reservoirs. Capryol 90, Tween 80, and Span 20 were finalized as suitable oil, surfactant, and co-surfactant, respectively, according to the pseudoternary phase diagram emulsifying region. Targeting capability and mucopenetration of the SNEDDS was attributed to the inclusion of amidated pluronic (NH2-F127). Developed NH2-F127 SNEDDS were characterized via physicochemical, in vitro, ex vivo, and in vivo evaluation parameters. The size of the SNEDDS was found to be 250 nm, having positively charged zeta potential. In vitro dissolution of SNEDDS showed 80% sustained release of CIP in 72 h with maximum entrapment efficiency up to 90% as well as good hemocompatibility by showing less than 0.2% hemolysis and 90% biocompatibility. The survival rate of S. typhi in macrophages (RAW 264.7) was minimal, i.e., only 2% in the case of NH2-F127 SNEDDS. Macrophage uptake assay via nanostructures confirmed the maximum cellular uptake as evidenced by the highest fluorescence. Biofilm dispersion assay showed rapid eradication of developed resistant biofilms on the gall bladder. In vivo pharmacokinetics showed improved bioavailability by showing an increased area under the curve (AUC) value. Taken together, NH2-F127-SNEDDS can be utilized as an alternative and efficient delivery system for the sustained release of therapeutic amounts of CIP for the treatment of S. typhi.

18.
Nanomaterials (Basel) ; 12(20)2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36296886

RESUMO

Graphene quantum dots (GQDs) have generated a great deal of scientific interest due to their bright fluorescence, good biocompatibility, minimal toxicity and fascinating physicochemical features. However, the ultimate issues regarding the acidic contaminations and high synthesis cost of GQDs remain open challenges for their real-world applications. Herein, we report an eco-friendly, acid-free and sustainable method for the preparation of GQDs using a cost-efficient, and renewable carbon source, 'biomass-waste', which simultaneously solves the risk of contamination from strong acids and high expenditure initiated by expensive precursors. The results demonstrate that GQDs possess a size range of 1-5 nm with an average size of ~3 ± 0.4 nm and a thickness of ~1 nm consisting of 1-3 layers of graphene. As-prepared GQDs demonstrate fascinating size-dependent optical properties and considerable surface grafting. Due to their intriguing optical properties, these GQDs are employed as fluorescence probes to detect ferric ions. A focused and sensitive sensor is developed with a detection limit down to 0.29 µM. This study emphasizes the need for using a reasonably green process and an inexpensive biomass precursor to create high-value GQDs that hold great potential for use in photocatalytic, bioimaging and real-world sensing applications.

19.
Front Immunol ; 13: 976677, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36045675

RESUMO

The tumour vasculature is well-established to display irregular structure and hierarchy that is conducive to promoting tumour growth and metastasis while maintaining immunosuppression. As tumours grow, their metabolic rate increases while their distance from blood vessels furthers, generating a hypoxic and acidic tumour microenvironment. Consequently, cancer cells upregulate the expression of pro-angiogenic factors which propagate aberrant blood vessel formation. This generates atypical vascular features that reduce chemotherapy, radiotherapy, and immunotherapy efficacy. Therefore, the development of therapies aiming to restore the vasculature to a functional state remains a necessary research target. Many anti-angiogenic therapies aim to target this such as bevacizumab or sunitinib but have shown variable efficacy in solid tumours due to intrinsic or acquired resistance. Therefore, novel therapeutic strategies such as combination therapies and nanotechnology-mediated therapies may provide alternatives to overcoming the barriers generated by the tumour vasculature. This review summarises the mechanisms that induce abnormal tumour angiogenesis and how the vasculature's features elicit immunosuppression. Furthermore, the review explores examples of treatment regiments that target the tumour vasculature.


Assuntos
Nanopartículas , Neoplasias , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Humanos , Imunoterapia , Nanopartículas/uso terapêutico , Neoplasias/metabolismo , Neovascularização Patológica/metabolismo , Microambiente Tumoral
20.
Biochim Biophys Acta Mol Basis Dis ; 1868(12): 166552, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36126898

RESUMO

The critical role of dysregulated epigenetic pathways in cancer genesis, development, and therapy has typically been established as a result of scientific and technical innovations in next generation sequencing. RNA interference, histone modification, DNA methylation and chromatin remodelling are epigenetic processes that control gene expression without causing mutations in the DNA. Although epigenetic abnormalities are thought to be a symptom of cell tumorigenesis and malignant events that impact tumor growth and drug resistance, physicians believe that related processes might be a key therapeutic target for cancer treatment and prevention due to the reversible nature of these processes. A plethora of novel strategies for addressing epigenetics in cancer therapy for immuno-oncological complications are currently available - ranging from basic treatment to epigenetic editing. - and they will be the subject of this comprehensive review. In this review, we cover most of the advancements made in the field of targeting epigenetics with special emphasis on microbiology, plasma science, biophysics, pharmacology, molecular biology, phytochemistry, and nanoscience.


Assuntos
Epigênese Genética , Neoplasias , Montagem e Desmontagem da Cromatina , Metilação de DNA , Epigenômica , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética
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