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1.
J Biochem Mol Toxicol ; 38(6): e23735, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38773908

RESUMO

Cancer is one of the major causes of death worldwide, with more than 10 million deaths annually. Despite tremendous advances in the health sciences, cancer continues to be a substantial global contributor to mortality. The current treatment methods demand a paradigm shift that not only improves therapeutic efficacy but also minimizes the side effects of conventional medications. Recently, an increased interest in the potential of natural bioactive compounds in the treatment of several types of cancer has been observed. Ononin, also referred to as formononetin-7-O-ß-d-glucoside, is a natural isoflavone glycoside, derived from the roots, stems, and rhizomes of various plants. It exhibits a variety of pharmacological effects, including Antiangiogenic, anti-inflammatory, antiproliferative, proapoptotic, and antimetastatic activities. The current review presents a thorough overview of sources, chemistry, pharmacokinetics, and the role of ononin in affecting various mechanisms involved in cancer. The review also discusses potential synergistic interactions with other compounds and therapies. The combined synergistic effect of ononin with other compounds increased the efficacy of treatment methods. Finally, the safety studies, comprising both in vitro and in vivo assessments of ononin's anticancer activities, are described.


Assuntos
Isoflavonas , Neoplasias , Isoflavonas/farmacologia , Isoflavonas/química , Isoflavonas/uso terapêutico , Humanos , Animais , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Glucosídeos/química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/uso terapêutico , Glicosídeos/farmacologia , Glicosídeos/uso terapêutico , Glicosídeos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química
2.
Naunyn Schmiedebergs Arch Pharmacol ; 397(1): 41-57, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37566307

RESUMO

Patients with glioblastoma multiforme and anaplastic astrocytoma are treated with temozolomide. Although it has been demonstrated that temozolomide increases GBM patient survival, it has also been connected to negative immune-related adverse effects. Numerous research investigations have shown that flavonoids have strong antioxidant and chemo-preventive effects. Consequently, it might lessen chemotherapeutic medicines' side effects while also increasing therapeutic effectiveness. The need for creating innovative, secure, and efficient drug carriers for cancer therapy has increased over time. Recent research indicates that exosomes have enormous potential to serve as carriers and cutting-edge drug delivery systems to the target cell. In recent years, researchers have been paying considerable attention to exosomes because of their favorable biodistribution, biocompatibility, and low immunogenicity. In the present review, the mechanistic information of the anti-glioblastoma effects of temozolomide and flavonoids coupled with their exosomal delivery to the targeted cell has been discussed. In addition, we discuss the safety aspects of temozolomide and flavonoids against glioma. The in-depth information of temozolomide and flavonoids action via exosomal delivery can unravel novel strategies to target Glioma.


Assuntos
Glioblastoma , Glioma , Humanos , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Distribuição Tecidual , Glioma/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico
3.
J Cancer Res Clin Oncol ; 149(19): 17709-17726, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37919474

RESUMO

BACKGROUND: Melittin is a water-soluble cationic peptide derived from bee venom that has been thoroughly studied for the cure of different cancers. However, the unwanted interactions of melittin produce hemolytic and cytotoxic effects that hinder their therapeutic applications. To overcome the shortcomings, numerous research groups have adopted different approaches, including conjugation with tumor-targeting proteins, gene therapy, and encapsulation in nanoparticles, to reduce the non-specific cytotoxic effects and potentiate their anti-cancerous activity. PURPOSE: This article aims to provide mechanistic insights into the chemopreventive activity of melittin and its nanoversion in combination with standard anti-cancer drugs for the treatment of cancer. METHODS: We looked over the pertinent research on melittin's chemopreventive properties in online databases such as PubMed and Scopus. CONCLUSION: In the present article, the anti-cancerous effects of melittin on different cancers have been discussed very nicely, as have their possible mechanisms of action to act against different tumors. Besides, it interacts with different signal molecules that regulate the diverse pathways of cancerous cells, such as cell cycle arrest, apoptosis, metastasis, angiogenesis, and inflammation. We also discussed the recent progress in the synergistic combination of melittin with standard anti-cancer drugs and a nano-formulated version of melittin for targeted delivery to improve its anticancer potential.


Assuntos
Antineoplásicos , Neoplasias , Animais , Meliteno/farmacologia , Meliteno/química , Meliteno/genética , Neoplasias/patologia , Antineoplásicos/uso terapêutico , Técnicas de Cultura de Células , Modelos Animais , Proliferação de Células
4.
J Mater Chem B ; 11(22): 4899-4913, 2023 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-37191118

RESUMO

Photodynamic therapy (PDT) is facing challenges such as poor solubility, precise delivery, self-aggregation, and photobleaching of photosensitizers with cancer cells due to their less tendency to accumulate in tumor tissues. To address these challenges, we have explored a Rose Bengal (RB)-loaded metallocatanionic vesicles (MCVs) nanosystem for the phototoxicity of cancer cells. Different sets of MCVs were prepared by two different cationic single-chain metallosurfactants, i.e., hexadecylpyridinium trichlorocuprate (CuCPC I) and hexadecylpyridinium trichloroferrate (FeCPC I) in combination with anionic double-chain sodium bis(2-ethylhexyl)sulfosuccinate (AOT) surfactant in phosphate buffer saline of pH 7.4. The RB-loaded CuCPC I:AOT and FeCPC I:AOT vesicles enhanced the maximum singlet oxygen (1O2) generation by 1-fold and 3-fold, respectively, compared to pure RB. Upon irradiation with a 532 nm laser for 10 min, these RB-loaded CuCPC I:AOT and FeCPC I:AOT MCVs significantly decreased the metabolic activity of U-251 cells by 70% and 85% at MCVs concentration of 0.75 µM, respectively. Furthermore, RB-loaded MCVs showed the highest intracellular 1O2-mediated membrane damage and cell-killing effect as confirmed by singlet oxygen sensor green and differential nuclear staining assay, which is attributed to the cellular uptake profile of different RB-loaded MCVs fractions. Caspase 3/7 assay confirmed the apoptotic pathway of cell death by activating caspase. Therefore, the photoactivation of RB-loaded MCVs led to a significant reduction in the viability of U-251 cells (maximum 85%), which resulted in cell death. Our study demonstrated the advantage of using these dual-charge and biocompatible metallocatanionic vesicles as a promising delivery system of photodynamic therapy that can enhance 1O2 generation from PS and can be further utilized in photomedicine.


Assuntos
Neoplasias , Fotoquimioterapia , Rosa Bengala/farmacologia , Oxigênio Singlete/metabolismo , Cetilpiridínio , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias/tratamento farmacológico
5.
Naunyn Schmiedebergs Arch Pharmacol ; 396(9): 1867-1878, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37010571

RESUMO

The Cucurbitaceae family produces a class of secondary metabolites known as cucurbitacins. The eight cucurbitacin subunits are cucurbitacin B, D, E, I, IIa, L glucoside, Q, and R with the most significant anticancer activity. They are reported to inhibit cell proliferation, invasion, and migration; induce apoptosis; and encourage cell cycle arrest, as some of their modes of action. The JAK-STAT3, Wnt, PI3K/Akt, and MAPK signaling pathways, which are essential for the survival and apoptosis of cancer cells, have also been shown to be suppressed by cucurbitacins. The goal of the current study is to summarize potential molecular targets that cucurbitacins could inhibit in order to suppress various malignant processes. The review is noteworthy since it presents all putative molecular targets for cucurbitacins in cancer on a single podium.


Assuntos
Neoplasias , Triterpenos , Humanos , Cucurbitacinas/farmacologia , Cucurbitacinas/uso terapêutico , Fosfatidilinositol 3-Quinases , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Apoptose , Proliferação de Células
6.
Pharmacol Res ; 186: 106523, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36377125

RESUMO

Despite advanced clinical and translational oncology research, mortality rates are still increasing worldwide. Recently, a class of non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have been well investigated in regulating biological, molecular, and cellular signaling pathways. This review article provided the current research progress on how miRNAs, lncRNAs, and circRNAs regulate Hedgehog (Hh) and Hippo signaling pathways in various cancers. These ncRNAs target both pathways' key downstream molecules and may be used for targeted cancer treatment. Moreover, Hh and Hippo signaling pathways crosstalked with each other through Gli1 of Hh pathways and YAP1/TEAD molecules of Hippo pathways during cancer progression. Additionally, Hh and Hippo signaling pathways regulate resistance against the chemo, radio, and immune therapies for several types of cancer via inducing GLI and YAP/TAZ proteins level. Therefore, to improve the treatment regime, we presented the role of various prominent phytochemicals such as curcumin, resveratrol, genistein, quercetin, paclitaxel, and silibinin in regulating lncRNAs, miRNAs, circRNA through Hedgehog and Hippo signaling pathways' constituents in cancers. We believe that knowledge obtained from this review may help make new drugs for cancer treatment in the future.


Assuntos
MicroRNAs , Neoplasias , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Circular , Proteínas Hedgehog , Via de Sinalização Hippo , RNA não Traduzido/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética
7.
Front Mol Neurosci ; 15: 921908, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35875669

RESUMO

Mitochondria provide neurons not only energy as ATP to keep them growing, proliferating and developing, but they also control apoptosis. Due to their high bioenergetic demand, neurons which are highly specific terminally differentiated cells, essentially depend on mitochondria. Defective mitochondrial function is thus related to numerous age-linked neurodegenerative ailments like Alzheimer's disease (AD), in which the build-up of impaired and malfunctioning mitochondria has been identified as a primary sign, paying to disease development. Mitophagy, selective autophagy, is a key mitochondrial quality control system that helps neurons to stay healthy and functional by removing undesired and damaged mitochondria. Dysfunctional mitochondria and dysregulated mitophagy have been closely associated with the onset of ADs. Various proteins associated with mitophagy were found to be altered in AD. Therapeutic strategies focusing on the restoration of mitophagy capabilities could be utilized to strike the development of AD pathogenesis. We summarize the mechanism and role of mitophagy in the onset and advancement of AD, in the quality control mechanism of mitochondria, the consequences of dysfunctional mitophagy in AD, and potential therapeutic approaches involving mitophagy modulation in AD. To develop new therapeutic methods, a better knowledge of the function of mitophagy in the pathophysiology of AD is required.

8.
Artigo em Inglês | MEDLINE | ID: mdl-35362379

RESUMO

The gut microbiota that comprises over 100 trillion microorganisms with a weight of about 1-2 kg is regarded as one of the most crucial players in the regulation of the metabolic health of host organisms. In recent years, the incidence of type 2 diabetes mellitus (T2DM), characterized by high levels of sugar in the blood, has been exponentially increasing due to obesity and other lifestyle risk factors. It was shown that dysbiosis, change in the overall composition, and diversity of gut microflora can result in T2DM. Conversely, the microbial composition can also influence the epigenetics of the host organism (DNA methylation as well as histone modifications), which might have a potential effect on the metabolic health of the individual. Another mechanism of gut microbiota in the development of T2DM is through the involvement of nucleotide-binding oligomerization domain, Leucine-rich Repeat, and Pyrin domain containing 3 (NLRP3) inflammasome, a part of the innate immune system. NLRP3 inflammasome produces inflammatory cytokines, promoting the secretion of microbial antigens in the intestinal epithelium. Therefore, it is important to understand the possible connecting link between gut microbiota and T2DM that might help in the modulation of gut microflora to better understand the disease. In this review, the role of gut microbiota in the pathogenesis of T2DM will be discussed.


Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Humanos , Inflamassomos/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Microbioma Gastrointestinal/fisiologia , Epigênese Genética
9.
ACS Biomater Sci Eng ; 8(5): 1878-1891, 2022 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-35412794

RESUMO

Photodynamic therapy (PDT) is an innovative technique for cancer treatment with minimal side effects, based on the use of a photosensitizer, oxygen, and light. Photosensitizers (PSs) have several limitations, that may limit their clinical use, like poor solubilization, self-aggregation, and lack of specific targeting, which can be addressed with the use of nanomaterials. Herein, a unique type of catansomes (CaSs) was prepared using a gemini imidazolium-based surfactant (1,3-bis[(3-octadecyl-1-imidazolio)methyl]benzene dibromide (GBIB) and a double chain surfactant, diaoctyl sodium sulfosuccinate or Aerosol OT (AOT). The formation of CaS GBIB/AOT was optimized in various ethanol/water (E/W) solvent ratios by employing a facile, quick, and most reliable solution-solution mixing method. The CaS was characterized by dynamic light scattering (DLS) and field emission gun scanning electron microscopy (FEG-SEM) techniques. The experimental results reveal that stable CaSs with a spherical shape were obtained at lower concentration (100 µM). Rose Bengal (RB), a PS of the xanthene family, was incorporated into these prepared CaSs, as proven by fluorescence spectroscopy, UV-visible absorption spectroscopy, and confocal laser scanning microscopy. Singlet oxygen (1O2) generation studies revealed the relevant role of the E/W solvent ratio as there was a 4-fold boost in the 1O2 production for GBIB/AOT in E/W = 50:50 and around 3-fold in E/W = 30:70. Also, the GBIB-rich 80:20 fraction was more efficient in increasing the 1O2 generation as compared to the AOT rich fraction (20:80). Further, their phototoxicity was tested in a water-rich solvent ratio (E/W = 30:70) against MCF-7 cells. Upon irradiation with a 532 nm laser (50 mW) for 5 min, RB@GBIB/AOT(20:80) fraction caused 50% decrease in the metabolic activity of MCF-7 cells, and RB@GBIB/AOT(80:20) fraction produced a maximum 85% decrease in cell viability. Furthermore, the enhancement in intracellular 1O2 generation by RB@GBIB/AOT, as compared to pure RB, was confirmed with singlet oxygen sensor green (SOSG). This new type of CaS based on gemini surfactants exhibiting a large amount of 1O2 generation, holds great interest for several applications, such as use in photomedicine in future.


Assuntos
Neoplasias , Rosa Bengala , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Rosa Bengala/química , Rosa Bengala/farmacologia , Rosa Bengala/uso terapêutico , Oxigênio Singlete/química , Oxigênio Singlete/uso terapêutico , Solventes/uso terapêutico , Tensoativos/farmacologia , Água
10.
J Mater Chem B ; 10(13): 2160-2170, 2022 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-35262166

RESUMO

In clinics, photodynamic therapy (PDT) is established as a non-invasive therapeutic modality for certain types of cancers and skin disease. However, due to poor water solubility, photobleaching, and the dark toxicity of photosensitizers (PSs), further developments are required to improve the efficiency of PDT. Herein, we report the role of metallocatanionic vesicles (MCVs) in enhancing the phototoxicity of methylene blue (MB) against cancer cells. These MCVs were prepared via a facile and quick solution-solution mixing method using a cationic single-chain metallosurfactant (FeCPC I) in combination with anionic sodium oleate (Na Ol). For singlet oxygen (1O2) generation and PDT studies, two fractions of FeCPC I : Na Ol, i.e., 30 : 70 (V37) and 70 : 30 (V73), were chosen based on their long-term stability in aqueous media. A cationic PS MB was loaded into these vesicles. The MB-loaded MCV 30 : 70 and 70 : 30 fractions enhanced the 1O2 generation by 0.10- and 0.40-fold, respectively, compared with MB alone. Upon illumination using a 650 nm laser, these MB-loaded V73 and V37 MCVs significantly decreased the metabolic activity of MCF-7 cells by ≤50% at a concentration of 0.75 µM. Furthermore, the SOSG assay revealed that the synthesized MCVs enhanced the intracellular 1O2 compared with MB alone. The MB-loaded V73 MCVs showed the highest 1O2-mediated membrane damage and cell-killing effect, as confirmed using the differential nuclear staining assay (DNS), which is attributed to the cellular uptake profile of the different MCV fractions. Altogether, this work shows the advantage of using these biocompatible and dual-charge MCVs as promising delivery vehicles that can enhance the 1O2 generation from the PS. This work suggests the future application of these Fe-MCVs in magnetically guided PDT.


Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Luz , Azul de Metileno/farmacologia , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Oxigênio Singlete/metabolismo
11.
Curr Dermatol Rep ; 11(2): 110-119, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35313686

RESUMO

Purpose of Review: Over a period of time, sporotrichosis has arisen as one of the leading fungal infections not only in animals but humans also. Several possible reasons that contribute to its emergence include change in epidemiology and distribution, evolutionary changes in taxonomy, and several outbreaks. World Health Organization has identified sporotrichosis as one of the major neglected tropical diseases (NTD) for 2021-2030 under the category of fungal NTDs. Several factors are contributing to increases in morbidity due to sporotrichosis such as delayed diagnosis and unavailability of appropriate antifungal therapy, which lead to redundant and inappropriate treatment with associate costs and adverse effects. Recent Findings: The potassium iodide is the first line of treatment for cutaneous forms while amphotericin B is used for the most severe cases of the disease. The limited medication arsenal, side effects, failure of therapy, and the advent of drug-resistant isolates emphasize the need for the development of new therapeutic options. Several studies are focusing on the development of the new drugs which either used alone or in combination with already available treatment. Along with this, several new antigens have been identified as possible targets for its vaccine development. Summary: The early diagnosis is required for selecting the best possible treatment strategy. The researchers should focus on developing new diagnostic methods and treatment options as well as vaccine development for the better management of sporotrichosis. In the long run, patient education for preventative features to reduce risk and counselling for prolonged therapy will be beneficial.

12.
Life Sci ; 284: 119901, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34453941

RESUMO

COVID-19 is a serious viral infection that struck the world in December 2019 starting from Wuhan in China, spreading subsequently to all over the world. The disease has baffled scientists and doctors worldwide in terms of its presentation, behaviour, and treatment options till now. A low mortality rate is the only relief we get so far from COVID-19 in terms of numbers. Treatment options have gradually streamlined to steroids and very few FDA approved antiviral as well as plasma therapy and supportive treatment. Monoclonal antibodies are used to tide over any impending cytokine storm but are not equally effective in all patients. Ventilation support is invariably required for moderate to severe disease varying from a simple High Flow non-rebreathing mask to BiPAP (Bilevel Positive Airway Pressure) and HFNO (High-Flow Nasal Oxygen) extending to full-fledge ventilation via a Mechanical Ventilator. Because of the non-availability of satisfactory treatment so far, many researchers from different biomedical fields are looking for alternative therapeutic strategies to manage the pandemic. One such therapeutic approach showing a ray of hope to combat COVID-19 infection is Mesenchymal stem cell therapy. Mesenchymal cells have immunomodulatory, anti-inflammatory as well as regenerative properties and various preliminary studies have shown that MSCs can reverse the lung damage and overcome the cytokine storm incited by COVID-19 infection. Also, it has improved the recovery rate of critically ill patients on mechanical ventilation. In this review, we will discuss the possibility and relevance of MSCs in COVID-19 treatment and preview of various MSCs clinical trials.


Assuntos
COVID-19/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , SARS-CoV-2/fisiologia , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/virologia , Ensaios Clínicos como Assunto , Humanos , Imunidade
13.
J Mater Chem B ; 8(40): 9304-9313, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-32966540

RESUMO

Currently, bacterial infection due to multi-drug-resistant bacteria is one of the foremost problems in public health. Photodynamic therapy plays a significant role against bacterial infection, without causing any side effects. But the photosensitizers are associated with many drawbacks, which lessen their photodynamic efficiency. In this context, the current study describes the synthesis of new metallocatanionic vesicles and employs them in photodynamic therapy. These vesicles were synthesized by using a single-chain cationic metallosurfactant (CuCPC I) and sodium oleate (NaOl) as an anionic component. These vesicles were characterized from conductivity, dynamic light scattering, zeta potential, field emission scanning electron microscopy, and confocal microscopy measurements. Methylene blue (MB) was used as a photosensitizer and its singlet oxygen quantum yield in the presence of these vesicles was determined by irradiating with 650 nm wavelength laser light. These vesicles play a dual-functional role, one helping in delivering the photosensitizer and the second doubling their singlet oxygen production capability due to the presence of metal ions. Antibacterial photodynamic therapy (aPDT) was studied against E. coli bacteria (Gram-negative bacteria). These vesicles also inherit their antibacterial activity and MB-encapsulated metallocatanionic vesicles on irradiation have shown 100% killing efficiency. In summary, we offer metallocatanionic vesicles prepared via a facile approach, which encapsulate a photosensitizer and can be used to combat E. coli infection through photodynamic therapy. We envisage that these synthesized metallocatanionic vesicles will provide a new modification to the catanionic mixture family and could be used for various applications in the future.


Assuntos
Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Lipossomos/química , Azul de Metileno/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Tensoativos/química , Antibacterianos/efeitos da radiação , Cetilpiridínio/química , Cobre/química , Escherichia coli/metabolismo , Luz , Azul de Metileno/efeitos da radiação , Testes de Sensibilidade Microbiana , Ácido Oleico/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/efeitos da radiação , Oxigênio Singlete/metabolismo
14.
Biomater Sci ; 8(10): 2905-2920, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32307486

RESUMO

Developments in the field of photodynamic therapy (PDT) are being made by investigating appropriate photosensitizers (PSs) and enhancing the penetration effect of light by developing new nano-carriers. So, to boost the PDT effect, in the present work, new metallocatanionic vesicles were fabricated by a convenient, efficient, green and inexpensive method to encapsulate PSs and evaluate their antimicrobial PDT against the drug-resistant bacterium Staphylococcus aureus. They were prepared from a combination of a double-chained copper-based cationic metallosurfactant (CuCPCII) and an anionic surfactant sodium bis(2-ethylhexyl)sulfosuccinate (Aerosol OT or AOT). The surface charge, structure and ability to encapsulate oppositely charged photosensitizers are some crucial factors that need to be controlled for their effective utilization in PDT. In this approach, two of the fractions, one each from a cationic rich and anionic rich side, were selected to encapsulate cationic (methylene blue; MB) and anionic (rose bengal (RB)) PSs after characterization by SAXS, AFM, FESEM, DLS, and zeta-potential, and conductivity measurements. Afterwards, PDT was performed on S. aureus (a multidrug-resistant bacterium) by the colony forming unit (CFU) method using PS encapsulated metallocatanionic vesicles that demonstrated high bactericidal activity by using visible light (532 nm) and facilitated the generation of singlet oxygen. The singlet oxygen generation capability of both the PSs was enhanced under irradiation when encapsulated in metallocatanionic vesicles because the presence of metal accelerated the intersystem crossing of triplet oxygen to singlet oxygen. Furthermore, these studies reveal that the metallocatanionic vesicles have dual functionality i.e. encapsulate PSs and even show dark toxicity against S. aureus. To study the killing of S. aureus, bacterial DNA was extracted and its interactions and conformational changes in the presence of metallocatanionic vesicles were analyzed via., UV-Visible, and circular dichroism (CD) spectroscopy. Comet assay (single-cell gel-electrophoresis) demonstrated the DNA damage after PDT treatment in an individual cell. The bacterial DNA damage was more with the metallosurfactant rich 70 : 30 fraction than with the 30 : 70 fraction, in combination with RB under irradiation. This work provides a new metal hybrid smart material that possesses dual functionality and is prepared by an easy, economical and feasible procedure which resulted in enhanced PDT against a drug-resistant bacterium, thus, providing an alternative for antibacterial therapy.


Assuntos
Antibacterianos/farmacologia , Compostos Organometálicos/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Tensoativos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Cápsulas/síntese química , Cápsulas/química , Cápsulas/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Tamanho da Partícula , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Propriedades de Superfície , Tensoativos/síntese química , Tensoativos/química
15.
ACS Appl Bio Mater ; 3(7): 4674-4683, 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35025466

RESUMO

Photodynamic therapy (PDT) has been extensively used as an effective alternative for the treatment of bacterial infection using photosensitizers (PSs) in the presence of appropriate light. However, the limitation in the effectiveness of PDT is because of the low yield of singlet oxygen from existing PSs because of their low solubility. Thus, we have developed a platform to enhance the solubility and the photodynamic activity of PSs against bacterial cells using metallosurfactants. Herein, we have used manganese metal-containing single- (MnC I) and double-chain metallosurfactants (MnC II) which show an interplay of electrostatic/hydrophobic interactions with fluorescein (FL) dye (as a PS) and when used in the presence of light enhances the PDT. These interactions play a significant role in enhancing the singlet oxygen generation efficiency of FL. MnC I and MnC II have shown good antimicrobial activity against Gram-positive Staphylococcus aureus (S. aureus) bacteria. More interestingly, these metallosurfactants when combined with FL significantly enhanced the affectivity against S. aureus, wherein 100% killing was achieved. As compared to experiments performed in the dark, the metallosurfactant, by enhancing the solubility of FL, increases the formation of singlet oxygen upon light irradiation and thus increases cell death. Therefore, the synergistic effect of FL (light toxicity) and metallosurfactants (dark toxicity) defined excellent reduction in the colony formation of bacteria. These results were corroborated through field-emission scanning electron microscopy and optical microscopy, where the rupturing of the cell wall of bacterial cells was observed during this therapy. Moreover, the binding of metallosurfactants to the genomic DNA of S. aureus was also evaluated by gel retardation analysis and UV-visible spectroscopy. The outcomes from this study will deliver formulations for PDT which can be used in clinical medical applications and cancer therapy in the future.

16.
ACS Appl Bio Mater ; 3(12): 8515-8524, 2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-35019621

RESUMO

Significant consumption of antibiotics has generated multidrug resistance in bacteria, which is a major menace to human beings. Antibacterial photodynamic therapy (aPDT) is a progressing technique for inhibition of bacterial infection with minimal side effects. Metals and delivering agents play a major role in aPDT efficiency. Herein, we report a formulation to enrich the antibacterial photodynamic therapy utilizing metallocatanionic vesicles (MCVs) against both Gram-positive and Gram-negative bacteria. These MCVs were synthesized by utilizing iron-based double-chain metallosurfactant [FeCPC(II)] as a cationic surfactant and AOT, a double-chain anionic surfactant. These synthesized MCV fractions were characterized by distinct techniques like DLS, zeta potential, FE-SEM, confocal microscopy, SAXS, and UV-Visible spectroscopy. Polyhedral-shaped MCVs with a size of 200 nm were formed, wherein the charge and size of the catanionic vesicle can be controlled by varying the mixing ratios. Both Gram-positive bacteria, i.e., methicillin-resistant Staphylococcus aureus (MRSA), and Gram-negative bacteria, i.e., Escherichia coli (E. coli), were used for aPDT using Rose Bengal (RB) as a photosensitizer (PS) encapsulated in MCVs in the presence of a 532 nm wavelength laser. The aPDT against bacterial cells was evaluated for both dark and light toxicities. Pure MCVs also exhibited good antibacterial properties; however, much enhancement was observed in the presence of RB encapsulated in MCVs under light, where eradication of bacteria (E. coli and MRSA) was achieved in 30 min. The observations demonstrated that it is the presence of metal that enhances the singlet oxygen quantum yield of RB and MCVs help in retarding self-quenching and enhanced solubilization of RB. The cationic surfactant-rich fraction shows strong adhesion toward bacteria via electrostatic interactions. The outcome of this research shows that these newly fabricated metal-based metallocatanionic vesicles were effective against both Gram-positive and Gram-negative bacteria using aPDT and must be exploited for clinical applications as well as an alternative for antibiotics in the future.

17.
J Food Sci Technol ; 54(6): 1577-1584, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28559617

RESUMO

This study describes the partial purification and characterization of lipoxygenase (LOX) from pearl millet mature grains of inbred HBL 0843-2. Two isoforms of LOX, i.e., LOX 1 and LOX 2, were purified using ammonium sulphate fractionation, gel filtration chromatography and ion exchange chromatography near homogeneity to 56 and 40 folds with yield of 28 and 24%, respectively. LOX 1 and LOX 2 having molecular masses of approximately 85 and 79 kDa, respectively were purified. LOX 1 and LOX 2 exhibited maximum activity at pH 4.5 and 4.8, respectively at 25 °C temperature. Both the isoforms, which showed thermostability up to 35 °C when incubated for 30 min, were stable at a pH range of 7-7.8. LOX 1 and LOX 2 had apparent Km value of 0.86 and 0.57 µM, respectively. Ascorbic acid and vitamin E inhibited 66-78 and 61-69% activity of LOX 1 and LOX 2, respectively but Na+, Zn2+ and K+ strongly inhibited the activity of these isozymes. The present information about lipoxygenase enzyme might be valuable in drafting the strategies for its inactivation, which in turn can obstruct the LOX damaging effects on food products during processing and storage.

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