Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 48.128
Filtrar
1.
BMC Biotechnol ; 24(1): 28, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38702622

RESUMO

Scientists know very little about the mechanisms underlying fish skin mucus, despite the fact that it is a component of the immune system. Fish skin mucus is an important component of defence against invasive infections. Recently, Fish skin and its mucus are gaining interest among immunologists. Characterization was done on the obtained silver nanoparticles Ag combined with Clarias gariepinus catfish epidermal mucus proteins (EMP-Ag-NPs) through UV-vis, FTIR, XRD, TEM, and SEM. Ag-NPs ranged in size from 4 to 20 nm, spherical in form and the angles were 38.10°, 44.20°, 64.40°, and 77.20°, Where wavelength change after formation of EMP-Ag-NPs as indicate of dark brown, the broad band recorded at wavelength at 391 nm. Additionally, the antimicrobial, antibiofilm and anticancer activities of EMP-Ag-NPs was assessed. The present results demonstrate high activity against unicellular fungi C. albicans, followed by E. faecalis. Antibiofilm results showed strong activity against both S. aureus and P. aeruginosa pathogens in a dose-dependent manner, without affecting planktonic cell growth. Also, cytotoxicity effect was investigated against normal cells (Vero), breast cancer cells (Mcf7) and hepatic carcinoma (HepG2) cell lines at concentrations (200-6.25 µg/mL) and current results showed highly anticancer effect of Ag-NPs at concentrations 100, 5 and 25 µg/mL exhibited rounding, shrinkage, deformation and granulation of Mcf7 and HepG2 with IC50 19.34 and 31.16 µg/mL respectively while Vero cells appeared rounded at concentration 50 µg/mL and normal shape at concentration 25, 12.5 and 6.25 µg/ml with IC50 35.85 µg/mL. This study evidence the potential efficacy of biologically generated Ag-NPs as a substitute medicinal agent against harmful microorganisms. Furthermore, it highlights their inhibitory effect on cancer cell lines.


Assuntos
Biofilmes , Peixes-Gato , Nanopartículas Metálicas , Prata , Nanopartículas Metálicas/química , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Prata/química , Prata/farmacologia , Animais , Humanos , Muco/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Células Vero , Proteínas de Peixes/farmacologia , Proteínas de Peixes/química , Proteínas de Peixes/metabolismo , Chlorocebus aethiops , Linhagem Celular Tumoral , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Candida albicans/efeitos dos fármacos , Epiderme/metabolismo
2.
Int J Nanomedicine ; 19: 3847-3859, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38708182

RESUMO

Background: Dihydroartemisinin (DHA) has emerged as a promising candidate for anticancer therapy. However, the application of DHA in clinics has been hampered by several limitations including poor bioavailability, short circulation life, and low solubility, significantly restricting its therapeutic efficacy and leading to notable side effects during the treatment. Purpose: We present DHA-loaded zeolitic imidazolate framework-8 (D-ZIF) with controllable and targeted DHA release properties, leading to enhanced antitumor effects while reducing potential side effects. Methods: D-ZIF was prepared by one-pot synthesis method using methylimidazole (MIM), Zn(NO3)2•6H2O and DHA. We characterized the physical and chemical properties of D-ZIF by TEM, DLS, XRD, FT-IR, and TG. We measured the drug loading efficiency and the cumulative release of DHA in different pH conditions. We evaluated the cytotoxicity of D-ZIF on renal cell carcinoma (RCC786-O), glioma cells (U251), TAX-resistant human lung adenocarcinoma (A549-TAX) cells by CCK8 in vitro. We explored the possible antitumor mechanism of D-ZIF by Western blot. We evaluated the biocompatibility and hemolysis of D-ZIF and explored the in vivo antitumor efficiency in mice model by TUNEL testing and blood biomarker evaluations. Results: D-ZIF showed rhombic dodecahedral morphology with size of 129±7.2 nm and possessed a noticeable DHA encapsulation efficiency (72.9%). After 48 hours, D-ZIF released a cumulative 70.0% of the loaded DHA at pH 6.5, and only 42.1% at pH 7.4. The pH-triggered programmed release behavior of D-ZIF could enhance anticancer effect of DHA while minimizing side effects under normal physiological conditions. Compared with the free DHA group with 31.75% of A549-TAX cell apoptosis, the percentage of apoptotic cells was approximately 76.67% in the D-ZIF group. D-ZIF inhibited tumor growth by inducing tumor cell apoptosis through the mechanism of ROS production and regulation of Nrf2/HO-1 and P38 MAPK signaling pathways. D-ZIF showed potent effects in treating tumors with high safety in vivo. Conclusion: This pH-responsive release mechanism enhanced the targeting efficiency of DHA towards tumor cells, thereby increasing drug concentration in tumor sites with negligible side effects. Herein, D-ZIF holds great promise for curing cancers with minimal adverse effects.


Assuntos
Antineoplásicos , Artemisininas , Resistencia a Medicamentos Antineoplásicos , Imidazóis , Neoplasias Pulmonares , Estruturas Metalorgânicas , Espécies Reativas de Oxigênio , Artemisininas/química , Artemisininas/farmacologia , Artemisininas/farmacocinética , Animais , Humanos , Espécies Reativas de Oxigênio/metabolismo , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacocinética , Estruturas Metalorgânicas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Camundongos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Linhagem Celular Tumoral , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/farmacocinética , Concentração de Íons de Hidrogênio , Células A549 , Liberação Controlada de Fármacos , Camundongos Nus , Apoptose/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Ensaios Antitumorais Modelo de Xenoenxerto , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Hemólise/efeitos dos fármacos
3.
Int J Nanomedicine ; 19: 3919-3942, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38708176

RESUMO

Typical physiological characteristics of tumors, such as weak acidity, low oxygen content, and upregulation of certain enzymes in the tumor microenvironment (TME), provide survival advantages when exposed to targeted attacks by drugs and responsive nanomedicines. Consequently, cancer treatment has significantly progressed in recent years. However, the evolution and adaptation of tumor characteristics still pose many challenges for current treatment methods. Therefore, efficient and precise cancer treatments require an understanding of the heterogeneity degree of various factors in cancer cells during tumor evolution to exploit the typical TME characteristics and manage the mutation process. The highly heterogeneous tumor and infiltrating stromal cells, immune cells, and extracellular components collectively form a unique TME, which plays a crucial role in tumor malignancy, including proliferation, invasion, metastasis, and immune escape. Therefore, the development of new treatment methods that can adapt to the evolutionary characteristics of tumors has become an intense focus in current cancer treatment research. This paper explores the latest understanding of cancer evolution, focusing on how tumors use new antigens to shape their "new faces"; how immune system cells, such as cytotoxic T cells, regulatory T cells, macrophages, and natural killer cells, help tumors become "invisible", that is, immune escape; whether the diverse cancer-associated fibroblasts provide support and coordination for tumors; and whether it is possible to attack tumors in reverse. This paper discusses the limitations of targeted therapy driven by tumor evolution factors and explores future strategies and the potential of intelligent nanomedicines, including the systematic coordination of tumor evolution factors and adaptive methods, to meet this therapeutic challenge.


Assuntos
Imunoterapia , Neoplasias , Microambiente Tumoral , Humanos , Microambiente Tumoral/efeitos dos fármacos , Imunoterapia/métodos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Neoplasias/imunologia , Nanomedicina/métodos , Animais , Nanopartículas/química , Antineoplásicos/química , Antineoplásicos/farmacologia
4.
Int J Nanomedicine ; 19: 3805-3825, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38708177

RESUMO

Telomere is a protective structure located at the end of chromosomes of eukaryotes, involved in maintaining the integrity and stability of the genome. Telomeres play an essential role in cancer progression; accordingly, targeting telomere dynamics emerges as an effective approach for the development of cancer therapeutics. Targeting telomere dynamics may work through multifaceted molecular mechanisms; those include the activation of anti-telomerase immune responses, shortening of telomere lengths, induction of telomere dysfunction and constitution of telomerase-responsive drug release systems. In this review, we summarize a wide variety of telomere dynamics-targeted agents in preclinical studies and clinical trials, and reveal their promising therapeutic potential in cancer therapy. As shown, telomere dynamics-active agents are effective as anti-cancer chemotherapeutics and immunotherapeutics. Notably, these agents may display efficacy against cancer stem cells, reducing cancer stem levels. Furthermore, these agents can be integrated with the capability of tumor-specific drug delivery by the constitution of related nanoparticles, antibody drug conjugates and HSA-based drugs.


Assuntos
Antineoplásicos , Neoplasias , Telomerase , Telômero , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Telômero/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Telomerase/antagonistas & inibidores , Animais , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Imunoterapia/métodos , Células-Tronco Neoplásicas/efeitos dos fármacos
5.
Carbohydr Polym ; 337: 122171, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38710561

RESUMO

Commercially available mushroom polysaccharides have found widespread use as adjuvant tumor treatments. However, the bioactivity of polysaccharides in Lactarius hatsudake Tanaka (L. hatsudake), a mushroom with both edible and medicinal uses, remains relatively unexplored. To address this gap, five L. hatsudake polysaccharides with varying molecular weights were isolated, named LHP-1 (898 kDa), LHP-2 (677 kDa), LHP-3 (385 kDa), LHP-4 (20 kDa), and LHP-5 (4.9 kDa). Gas chromatography-mass spectrometry, nuclear magnetic resonance, and atomic force microscopy, etc., were employed to determine their structural characteristics. The results confirmed that spherical aggregates with amorphous flexible fiber chains dominated the conformation of the LHP. LHP-1 and LHP-2 were identified as glucans with α-(1,4)-Glcp as the main chain; LHP-3 and LHP-4 were classified as galactans with varying molecular weights but with α-(1,6)-Galp as the main chain; LHP-5 was a glucan with ß-(1,3)-Glcp as the main chain and ß-(1,6)-Glcp connecting to the side chains. Significant differences were observed in inhibiting tumor cell cytotoxicity and the antioxidant activity of the LHPs, with LHP-5 and LHP-4 identified as the principal bioactive components. These findings provide a theoretical foundation for the valuable use of L. hatsudake and emphasize the potential application of LHPs in therapeutic tumor treatments.


Assuntos
Antioxidantes , Glucanos , Glucanos/química , Glucanos/farmacologia , Glucanos/isolamento & purificação , Humanos , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/isolamento & purificação , Agaricales/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Polissacarídeos/isolamento & purificação , Peso Molecular , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/farmacologia , Polissacarídeos Fúngicos/isolamento & purificação , Basidiomycota/química , Sobrevivência Celular/efeitos dos fármacos
6.
AAPS PharmSciTech ; 25(5): 97, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710894

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the highly fatal types of cancer with high mortality/incidence. Considering the crucial role of vascular endothelial growth factor (VEGF) in PDAC progression, its inhibition can be a viable strategy for the treatment. Pazopanib, a second-generation VEGF inhibitor, is approved for the treatment of various oncological conditions. However, due to associated limitations like low oral bioavailability (14-39%), high inter/intra-subject variability, stability issues, etc., high doses (800 mg) are required, which further lead to non-specific toxicities and also contribute toward cancer resistance. Thus, to overcome these challenges, pazopanib-loaded PEGylated nanoliposomes were developed and evaluated against pancreatic cancer cell lines. The nanoliposomes were prepared by thin-film hydration method, followed by characterization and stability studies. This QbD-enabled process design successfully led to the development of a suitable pazopanib liposomal formulation with desirable properties. The % entrapment of PZP-loaded non-PEGylated and PEGylated nanoliposomes was found to be 75.2% and 84.9%, respectively, whereas their particle size was found to be 129.7 nm and 182.0 nm, respectively. The developed liposomal formulations exhibited a prolonged release and showed desirable physicochemical properties. Furthermore, these liposomal formulations were also assessed for in vitro cell lines, such as cell cytotoxicity assay and cell uptake. These studies confirm the effectiveness of developed liposomal formulations against pancreatic cancer cell lines. The outcomes of this work provide encouraging results and a way forward to thoroughly investigate its potential for PDAC treatment.


Assuntos
Carcinoma Ductal Pancreático , Indazóis , Lipossomos , Nanopartículas , Neoplasias Pancreáticas , Tamanho da Partícula , Pirimidinas , Sulfonamidas , Indazóis/administração & dosagem , Indazóis/farmacologia , Humanos , Sulfonamidas/administração & dosagem , Sulfonamidas/farmacologia , Sulfonamidas/química , Pirimidinas/administração & dosagem , Pirimidinas/farmacologia , Pirimidinas/química , Pirimidinas/farmacocinética , Linhagem Celular Tumoral , Neoplasias Pancreáticas/tratamento farmacológico , Carcinoma Ductal Pancreático/tratamento farmacológico , Nanopartículas/química , Polietilenoglicóis/química , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Química Farmacêutica/métodos
7.
Chem Biol Drug Des ; 103(5): e14536, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38725079

RESUMO

This research was designed to prospect the mechanism and impact of glycyrrhizic acid (GA) on DNA damage repair and cisplatin (CP)-induced apoptosis of melanoma cells. First, human melanoma cell SK-MEL-28 was stimulated using GA for 24, 48, and 72 h. Then, the optimal treatment time and dosage were selected. After that, cell counting kit-8 (CCK-8) was employed for testing the cell viability, flow cytometry for the apoptosis, comet assay for the DNA damage of cells, and western blot for the cleaved-Caspase3, Caspase3, Bcl-2, and γH2AX protein expression levels. The experimental outcomes exhibited that as the GA concentration climbed up, the SK-MEL-28 cell viability dropped largely, while the apoptosis level raised significantly, especially at the concentration of 100 µm. In addition, compared with GA or CPtreatment only, CP combined with GA notably suppressed the viability of melanoma cells and promoted cell apoptosis at the cytological level. At the protein level, the combined treatment notably downregulated the Bcl-2 and Caspase3 expression levels, while significantly upregulated the cleaved-Caspase3 and γH2AX expression levels. Besides, CP + GA treatment promoted DNA damage at the DNA molecular level. Collectively, both GA and CP can inhibit DNA damage repair and enhance the apoptosis of SK-MEL-28 cells, and the synergistic treatment of both exhibits better efficacy.


Assuntos
Apoptose , Cisplatino , Dano ao DNA , Reparo do DNA , Ácido Glicirrízico , Melanoma , Cisplatino/farmacologia , Humanos , Ácido Glicirrízico/farmacologia , Ácido Glicirrízico/química , Apoptose/efeitos dos fármacos , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Melanoma/patologia , Linhagem Celular Tumoral , Dano ao DNA/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Caspase 3/metabolismo , Sinergismo Farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
8.
J Sep Sci ; 47(9-10): e2300898, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38726747

RESUMO

Based on the specific binding of drug molecules to cell membrane receptors, a screening and separation method for active compounds of natural products was established by combining phospholipase C (PLC) sensitized hollow fiber microscreening by a solvent seal with high-performance liquid chromatography technology. In the process, the factors affecting the screening were optimized. Under the optimal screening conditions, we screened honokiol (HK), magnolol (MG), negative control drug carbamazepine, and positive control drug amentoflavone, the repeatability of the method was tested. The PLC activity was determined before and after the screening. Experimental results showed that the sensitization factors of PLC of HK and MG were 61.0 and 48.5, respectively, and amentoflavone was 15.0, carbamazepine could not bind to PLC. Moreover, the molecular docking results were consistent with this measurement, indicating that HK and MG could be combined with PLC, and they were potential interacting components with PLC. This method used organic solvent to seal the PLC greatly ensuring the activity, so this method had the advantage of integrating separation, and purification with screening, it not only exhibited good reproducibility and high sensitivity but was also suitable for screening the active components in natural products by various targets in vitro.


Assuntos
Produtos Biológicos , Fosfolipases Tipo C , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Produtos Biológicos/isolamento & purificação , Fosfolipases Tipo C/metabolismo , Fosfolipases Tipo C/química , Fosfolipases Tipo C/antagonistas & inibidores , Cromatografia Líquida de Alta Pressão , Simulação de Acoplamento Molecular , Lignanas/química , Lignanas/isolamento & purificação , Lignanas/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/isolamento & purificação , Humanos , Compostos Alílicos , Fenóis
9.
Chem Biol Drug Des ; 103(5): e14531, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38726798

RESUMO

Inhibition of prolylhydroxylase-2 (PHD-2) in both normoxic and hypoxic cells is a critical component of solid tumours. The present study aimed to identify small molecules with PHD-2 activation potential. Virtually screening 4342 chemical compounds for structural similarity to R59949 and docking with PHD-2. To find the best drug candidate, hits were assessed for drug likeliness, antihypoxic and antineoplastic potential. The selected drug candidate's PHD-2 activation, cytotoxic and apoptotic potentials were assessed using 2-oxoglutarate, MTT, AO/EtBr and JC-1 staining. The drug candidate was also tested for its in-vivo chemopreventive efficacy against DMBA-induced mammary gland cancer alone and in combination with Tirapazamine (TPZ). Virtual screening and 2-oxoglutarate assay showed BBAP-6 as lead compound. BBAP-6 exhibited cytotoxic and apoptotic activity against ER+ MCF-7. In carmine staining and histology, BBAP-6 alone or in combination with TPZ restored normal surface morphology of the mammary gland after DMBA produced malignant alterations. Immunoblotting revealed that BBAP-6 reduced NF-κB expression, activated PHD-2 and induced intrinsic apoptotic pathway. Serum metabolomics conducted with 1H NMR confirmed that BBAP-6 prevented HIF-1α and NF-κB-induced metabolic changes in DMBA mammary gland cancer model. In a nutshell, it can be concluded that BBAP-6 activates PHD-2 and exhibits anticancer potential.


Assuntos
Apoptose , Neoplasias da Mama , Prolina Dioxigenases do Fator Induzível por Hipóxia , Humanos , Feminino , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/prevenção & controle , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Prolina Dioxigenases do Fator Induzível por Hipóxia/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Camundongos , Hipóxia Celular/efeitos dos fármacos , Simulação de Acoplamento Molecular , Antineoplásicos/farmacologia , Antineoplásicos/química , Células MCF-7 , Linhagem Celular Tumoral , NF-kappa B/metabolismo , Tirapazamina/farmacologia , Tirapazamina/química , Tirapazamina/metabolismo
10.
Med Oncol ; 41(6): 145, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727885

RESUMO

Polyelectrolytes represent a unique class of polymers abundant in ionizable functional groups. In a solution, ionized polyelectrolytes can intricately bond with oppositely charged counterparts, giving rise to a fascinating phenomenon known as a polyelectrolyte complex. These complexes arise from the interaction between oppositely charged entities, such as polymers, drugs, and combinations thereof. The polyelectrolyte complexes are highly appealing in cancer management, play an indispensable role in chemotherapy, crafting biodegradable, biocompatible 3D membranes, microcapsules, and nano-sized formulations. These versatile complexes are pivotal in designing controlled and targeted release drug delivery systems. The present review emphasizes on classification of polyelectrolyte complex along with their formation mechanisms. This review comprehensively explores the applications of polyelectrolyte complex, highlighting their efficacy in targeted drug delivery strategies for combating different forms of cancer. The innovative use of polyelectrolyte complex presents a potential breakthrough in cancer therapeutics, demonstrating their role in enhancing treatment precision and effectiveness.


Assuntos
Antineoplásicos , Sistemas de Liberação de Medicamentos , Neoplasias , Polieletrólitos , Humanos , Polieletrólitos/química , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Medicina de Precisão/métodos
11.
Int J Nanomedicine ; 19: 3891-3905, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711613

RESUMO

Introduction: The synthesis of nanoparticles using naturally occurring reagents such as vitamins, sugars, plant extracts, biodegradable polymers and microorganisms as reductants and capping agents could be considered attractive for nanotechnology. These syntheses have led to the fabrication of limited number of inorganic nanoparticles. Among the reagents mentioned above, plant-based materials seem to be the best candidates, and they are suitable for large-scale biosynthesis of nanoparticles. Methods: The aqueous extract of Moringa peregrina leaves was used to synthesize silver nanoparticles. The synthesized nanoparticles were characterized by various spectral studies including FT-IR, SEM, HR-TEM and XRD. In addition, the antioxidant activity of the silver nanoparticles was studied viz. DPPH, ABTS, hydroxyl radical scavenging, superoxide radical scavenging, nitric oxide scavenging potential and reducing power with varied concentrations. The anticancer potential of the nanoparticles was also studied against MCF-7 and Caco-2 cancer cell lines. Results: The results showed that silver nanoparticles displayed strong antioxidant activity compared with gallic acid. Furthermore, the anticancer potential of the nanoparticles against MCF-7 and Caco-2 in comparison with the standard Doxorubicin revealed that the silver nanoparticles produced significant toxic effects against the studied cancer cell lines with the IC50 values of 41.59 (Caco-2) and 26.93 (MCF-7) µg/mL. Conclusion: In conclusion, the biosynthesized nanoparticles using M. peregrina leaf aqueous extract as a reducing agent showed good antioxidant and anticancer potential on human cancer cells and can be used in biological applications.


Assuntos
Antioxidantes , Química Verde , Nanopartículas Metálicas , Moringa , Extratos Vegetais , Folhas de Planta , Prata , Humanos , Prata/química , Prata/farmacologia , Nanopartículas Metálicas/química , Células MCF-7 , Células CACO-2 , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Moringa/química , Antioxidantes/farmacologia , Antioxidantes/química , Folhas de Planta/química , Sobrevivência Celular/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química
12.
Int J Nanomedicine ; 19: 3957-3972, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711614

RESUMO

Purpose: Current treatment approaches for Prostate cancer (PCa) often come with debilitating side effects and limited therapeutic outcomes. There is urgent need for an alternative effective and safe treatment for PCa. Methods: We developed a nanoplatform to target prostate cancer cells based on graphdiyne (GDY) and a copper-based metal-organic framework (GDY-CuMOF), that carries the chemotherapy drug doxorubicin (DOX) for cancer treatment. Moreover, to provide GDY-CuMOF@DOX with homotypic targeting capability, we coated the PCa cell membrane (DU145 cell membrane, DCM) onto the surface of GDY-CuMOF@DOX, thus obtaining a biomimetic nanoplatform (DCM@GDY-CuMOF@DOX). The nanoplatform was characterized by using transmission electron microscope, atomic force microscope, X-ray diffraction, etc. Drug release behavior, antitumor effects in vivo and in vitro, and biosafety of the nanoplatform were evaluated. Results: We found that GDY-CuMOF exhibited a remarkable capability to load DOX mainly through π-conjugation and pore adsorption, and it responsively released DOX and generated Cu+ in the presence of glutathione (GSH). In vivo experiments demonstrated that this nanoplatform exhibits remarkable cell-killing efficiency by generating lethal reactive oxygen species (ROS) and mediating cuproptosis. In addition, DCM@GDY-CuMOF@DOX effectively suppresses tumor growth in vivo without causing any apparent side effects. Conclusion: The constructed DCM@GDY-CuMOF@DOX nanoplatform integrates tumor targeting, drug-responsive release and combination with cuproptosis and chemodynamic therapy, offering insights for further biomedical research on efficient PCa treatment.


Assuntos
Cobre , Doxorrubicina , Grafite , Estruturas Metalorgânicas , Neoplasias da Próstata , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Doxorrubicina/farmacologia , Doxorrubicina/química , Animais , Humanos , Linhagem Celular Tumoral , Cobre/química , Cobre/farmacologia , Grafite/química , Grafite/farmacologia , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Camundongos , Liberação Controlada de Fármacos , Espécies Reativas de Oxigênio/metabolismo , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Camundongos Nus , Nanopartículas/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Portadores de Fármacos/química , Ensaios Antitumorais Modelo de Xenoenxerto
13.
PLoS One ; 19(5): e0302276, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38713692

RESUMO

Based on topological descriptors, QSPR analysis is an incredibly helpful statistical method for examining many physical and chemical properties of compounds without demanding costly and time-consuming laboratory tests. Firstly, we discuss and provide research on kidney cancer drugs using topological indices and done partition of the edges of kidney cancer drugs which are based on the degree. Secondly, we examine the attributes of nineteen drugs casodex, eligard, mitoxanrone, rubraca, and zoladex, etc and among others, using linear QSPR model. The study in the article not only demonstrates a good correlation between TIs and physical characteristics with the QSPR model being the most suitable for predicting complexity, enthalpy, molar refractivity, and other factors and a best-fit model is attained in this study. This theoretical approach might benefit chemists and professionals in the pharmaceutical industry to forecast the characteristics of kidney cancer therapies. This leads towards new opportunities to paved the way for drug discovery and the formation of efficient and suitable treatment options in therapeutic targeting. We also employed multicriteria decision making techniques like COPRAS and PROMETHEE-II for ranking of said disease treatment drugs and physicochemical characteristics.


Assuntos
Antineoplásicos , Neoplasias Renais , Relação Quantitativa Estrutura-Atividade , Neoplasias Renais/tratamento farmacológico , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Humanos , Tomada de Decisões , Descoberta de Drogas/métodos
14.
Int J Nanomedicine ; 19: 4007-4019, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38715701

RESUMO

Introduction: Nanosized outer membrane vesicles (OMVs) from Gram-negative bacteria have attracted increasing interest because of their antitumor activity. However, the antitumor effects of MVs isolated from Gram-positive bacteria have rarely been investigated. Methods: MVs of Staphylococcus aureus USA300 were prepared and their antitumor efficacy was evaluated using tumor-bearing mouse models. A gene knock-in assay was performed to generate luciferase Antares2-MVs for bioluminescent detection. Cell counting kit-8 and lactic dehydrogenase release assays were used to detect the toxicity of the MVs against tumor cells in vitro. Active caspase-1 and gasdermin D (GSDMD) levels were determined using Western blot, and the tumor inhibition ability of MVs was determined in B16F10 cells treated with a caspase-1 inhibitor. Results: The vesicular particles of S. aureus USA300 MVs were 55.23 ± 8.17 nm in diameter, and 5 µg of MVs remarkably inhibited the growth of B16F10 melanoma in C57BL/6 mice and CT26 colon adenocarcinoma in BALB/c mice. The bioluminescent signals correlated well with the concentrations of the engineered Antares2-MVs (R2 = 0.999), and the sensitivity for bioluminescence imaging was 4 × 10-3 µg. Antares2-MVs can directly target tumor tissues in vivo, and 20 µg/mL Antares2-MVs considerably reduced the growth of B16F10 and CT26 tumor cells, but not non-carcinomatous bEnd.3 cells. MV treatment substantially increased the level of active caspase-1, which processes GSDMD to trigger pyroptosis in tumor cells. Blocking caspase-1 activation with VX-765 significantly protected tumor cells from MV killing in vitro and in vivo. Conclusion: S. aureus MVs can kill tumor cells by activating the pyroptosis pathway, and the induction of pyroptosis in tumor cells is a promising strategy for cancer treatment.


Assuntos
Caspase 1 , Camundongos Endogâmicos BALB C , Piroptose , Staphylococcus aureus , Animais , Piroptose/efeitos dos fármacos , Caspase 1/metabolismo , Linhagem Celular Tumoral , Staphylococcus aureus/fisiologia , Staphylococcus aureus/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Proteínas de Ligação a Fosfato/metabolismo , Melanoma Experimental/patologia , Neoplasias do Colo , Antineoplásicos/farmacologia , Antineoplásicos/química , Membrana Externa Bacteriana/efeitos dos fármacos , Feminino
15.
Sci Rep ; 14(1): 10561, 2024 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719884

RESUMO

This study focuses on understanding the structural and molecular changes in lipid membranes under the influence of six halogenated flavonoid derivatives differing in the number and position of substitution of chlorine and bromine atoms (D1-D6). Utilizing various analytical techniques, including fluorometric methods, dynamic light scattering (DLS), attenuated Fourier transform infrared spectroscopy (ATR- FTIR), and FT-Raman spectroscopy, the research aims to elucidate the mechanisms underlying the interaction of flavonoids with cell membranes. Additionally, the study includes in silico analyses to explore the physicochemical properties of these compounds and their potential pharmaceutical applications, along with toxicity studies to assess their effects on cancer, normal, and red blood cells. Our study showed the ability of halogenated derivatives to interact mostly with the outer part of the membrane, especially in the lipid heads region however, some of them were able to penetrate deeper into the membrane and affect the fluidity of hydrocarbon chains. The potential to reduce cancer cell viability, the lack of toxicity towards erythrocytes, and the favourable physicochemical and pharmacokinetic properties suggest these halogenated flavonoids potential candidates for exploring their potential for medical use.


Assuntos
Flavonoides , Lipídeos de Membrana , Flavonoides/química , Flavonoides/farmacologia , Flavonoides/metabolismo , Humanos , Lipídeos de Membrana/metabolismo , Lipídeos de Membrana/química , Membrana Celular/metabolismo , Halogenação , Citotoxinas/química , Citotoxinas/farmacologia , Citotoxinas/metabolismo , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Análise Espectral Raman , Espectroscopia de Infravermelho com Transformada de Fourier , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/metabolismo , Linhagem Celular Tumoral
16.
Biomed Mater ; 19(4)2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38697132

RESUMO

During the process of malignant tumor treatment, photodynamic therapy (PDT) exerts poor efficacy due to the hypoxic environment of the tumor cells, and long-time chemotherapy reduces the sensitivity of tumor cells to chemotherapy drugs due to the presence of drug-resistant proteins on the cell membranes for drug outward transportation. Therefore, we reported a nano platform based on mesoporous silica coated with polydopamine (MSN@PDA) loading PDT enhancer MnO2, photosensitizer indocyanine green (ICG) and chemotherapeutic drug doxorubicin (DOX) (designated as DMPIM) to achieve a sequential release of different drugs to enhance treatment of malignant tumors. MSN was first synthesized by a template method, then DOX was loaded into the mesoporous channels of MSN, and locked by the PDA coating. Next, ICG was modified by π-π stacking on PDA, and finally, MnO2layer was accumulated on the surface of DOX@MSN@PDA- ICG@MnO2, achieving orthogonal loading and sequential release of different drugs. DMPIM first generated oxygen (O2) through the reaction between MnO2and H2O2after entering tumor cells, alleviating the hypoxic environment of tumors and enhancing the PDT effect of sequentially released ICG. Afterwards, ICG reacted with O2in tumor tissue to produce reactive oxygen species, promoting lysosomal escape of drugs and inactivation of p-glycoprotein (p-gp) on tumor cell membranes. DOX loaded in the MSN channels exhibited a delay of approximately 8 h after ICG release to exert the enhanced chemotherapy effect. The drug delivery system achieved effective sequential release and multimodal combination therapy, which achieved ideal therapeutic effects on malignant tumors. This work offers a route to a sequential drug release for advancing the treatment of malignant tumors.


Assuntos
Doxorrubicina , Liberação Controlada de Fármacos , Verde de Indocianina , Indóis , Compostos de Manganês , Óxidos , Fotoquimioterapia , Fármacos Fotossensibilizantes , Polímeros , Fotoquimioterapia/métodos , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/administração & dosagem , Verde de Indocianina/química , Indóis/química , Animais , Compostos de Manganês/química , Humanos , Polímeros/química , Linhagem Celular Tumoral , Óxidos/química , Fármacos Fotossensibilizantes/química , Dióxido de Silício/química , Camundongos , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Neoplasias/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Portadores de Fármacos/química , Porosidade
17.
Sci Rep ; 14(1): 10499, 2024 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714740

RESUMO

Improving the efficacy of chemotherapy remains a key challenge in cancer treatment, considering the low bioavailability, high cytotoxicity, and undesirable side effects of some clinical drugs. Targeted delivery and sustained release of therapeutic drugs to cancer cells can reduce the whole-body cytotoxicity of the agent and deliver a safe localized treatment to the patient. There is growing interest in herbal drugs, such as curcumin, which is highly noted as a promising anti-tumor drug, considering its wide range of bioactivities and therapeutic properties against various tumors. Conversely, the clinical efficacy of curcumin is limited because of poor oral bioavailability, low water solubility, instability in gastrointestinal fluids, and unsuitable pH stability. Drug-delivery colloid vehicles like liposomes and nanoparticles combined with microbubbles and ultrasound-mediated sustained release are currently being explored as effective delivery modes in such cases. This study aimed to synthesize and study the properties of curcumin liposomes (CLs) and optimize the high-frequency ultrasound release and uptake by a human breast cancer cell line (HCC 1954) through in vitro studies of culture viability and cytotoxicity. CLs were effectively prepared with particles sized at 81 ± 2 nm, demonstrating stability and controlled release of curcumin under ultrasound exposure. In vitro studies using HCC1954 cells, the combination of CLs, ultrasound, and Definity microbubbles significantly improved curcumin's anti-tumor effects, particularly under specific conditions: 15 s of continuous ultrasound at 0.12 W/cm2 power density with 0.6 × 107 microbubbles/mL. Furthermore, the study delved into curcumin liposomes' cytotoxic effects using an Annexin V/PI-based apoptosis assay. The treatment with CLs, particularly in conjunction with ultrasound and microbubbles, amplified cell apoptosis, mainly in the late apoptosis stage, which was attributed to heightened cellular uptake within cancer cells.


Assuntos
Curcumina , Sistemas de Liberação de Medicamentos , Lipossomos , Curcumina/farmacologia , Curcumina/química , Curcumina/administração & dosagem , Humanos , Lipossomos/química , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Sobrevivência Celular/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Microbolhas , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Ondas Ultrassônicas , Liberação Controlada de Fármacos , Apoptose/efeitos dos fármacos
18.
Sci Rep ; 14(1): 10117, 2024 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698033

RESUMO

In this research, the hydrophilic structure of multi-walled carbon nanotubes (MWCNTs) was modified by synthesizing polycitric acid (PCA) and attaching folic acid (FA) to create MWCNT-PCA-FA. This modified nanocomplex was utilized as a carrier for the lipophilic compound curcumin (Cur). Characterization techniques including TGA, TEM, and UV-visible spectrophotometry were used to analyze the nanocomplex. The mechanism of cancer cell death induced by MWCNT-PCA-FA was studied extensively using the MTT assay, colony formation analysis, cell cycle assessment via flow cytometry, and apoptosis studies. Furthermore, we assessed the antitumor efficacy of these targeted nanocomplexes following exposure to laser radiation. The results showed that the nanocomposites and free Cur had significant toxicity on melanoma cancer cells (B16F10 cells) while having minimal impact on normal cells (NHDF cells). This selectivity for cancerous cells demonstrates the potential of these compounds as therapeutic agents. Furthermore, MWCNT-PCA-FA/Cur showed superior cytotoxicity compared to free Cur alone. Colony formation studies confirmed these results. The researchers found that MWCNT-FA-PCA/Cur effectively induced programmed cell death. In photothermal analysis, MWCNT-PCA-FA/Cur combined with laser treatment achieved the highest mortality rate. These promising results suggest that this multifunctional therapeutic nanoplatform holds the potential for combination cancer therapies that utilize various established therapeutic methods.


Assuntos
Curcumina , Nanotubos de Carbono , Curcumina/farmacologia , Curcumina/química , Nanotubos de Carbono/química , Linhagem Celular Tumoral , Humanos , Camundongos , Animais , Ácido Fólico/química , Apoptose/efeitos dos fármacos , Melanoma/tratamento farmacológico , Melanoma/patologia , Melanoma/terapia , Terapia Fototérmica/métodos , Antineoplásicos/farmacologia , Antineoplásicos/química , Portadores de Fármacos/química , Sobrevivência Celular/efeitos dos fármacos
19.
Sci Rep ; 14(1): 10284, 2024 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704421

RESUMO

The use of magnetic metal nanoparticles has been considered in cancer treatment studies. In this study, BiFe2O4@Ag nanoparticles were synthesized biologically by Scenedesmus obliquus for the first time and their anticancer mechanism in a gastric cancer cell line was characterized. The physicochemical properties of the nanoparticles were evaluated by fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic Light Scattering (DLS), and zeta potential analyses. Cell viability and nuclear damage were investigated by the MTT and Hoechst staining assays, respectively. Flow cytometry analysis was performed to determine the frequency of the necrotic and apoptotic cells as well as cell cycle analysis of the nanoparticles-treated cells. Physicochemical characterization showed that the synthesized particles were spherical, without impurities, in a size range of 38-83 nm, with DLS size and zeta potential of 295.7 nm and -27.7 mV, respectively. BiFe2O4@Ag nanoparticles were considerably more toxic for the gastric cancer cells (AGS cell line) than HEK293 normal cells with IC50 of 67 and 117 µg/ml, respectively. Treatment of AGS cells with the nanoparticles led to a remarkable increase in the percentage of late apoptosis (38.5 folds) and cell necrosis (13.4 folds) and caused cell cycle arrest, mainly at the S phase. Also, nuclear fragmentation and apoptotic bodies were observed in the gastric cancer cells treated with the nanoparticles. This study represents BiFe2O4@Ag as a novel anticancer candidate against gastric cancer that can induce cell apoptosis through DNA damage and inhibition of cell cycle progression.


Assuntos
Apoptose , Nanopartículas Metálicas , Scenedesmus , Prata , Neoplasias Gástricas , Humanos , Apoptose/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Linhagem Celular Tumoral , Nanopartículas Metálicas/química , Scenedesmus/efeitos dos fármacos , Prata/química , Prata/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Células HEK293 , Difração de Raios X
20.
Sci Rep ; 14(1): 10406, 2024 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710736

RESUMO

Active pharmaceutical ingredients have emerged as an environmentally undesirable element because of their widespread exploitation and consequent pollution, which has deleterious effects on living things. In the pursuit of sustainable environmental remediation, biomedical applications, and energy production, there has been a significant focus on two-dimensional materials (2D materials) owing to their unique electrical, optical, and structural properties. Herein, we have synthesized 2D zinc oxide nanosheets (ZnO NSs) using a facile and practicable hydrothermal method and characterized them thoroughly using spectroscopic and microscopic techniques. The 2D nanosheets are used as an efficient photocatalyst for antibiotic (herein, end-user ciprofloxacin (CIP) was used as a model antibiotic) degradation under sunlight. It is observed that ZnO NSs photodegrade ~ 90% of CIP within two hours of sunlight illumination. The molecular mechanism of CIP degradation is proposed based on ex-situ IR analysis. Moreover, the 2D ZNO NSs are used as an antimicrobial agent and exhibit antibacterial qualities against a range of bacterial species, including Escherichia coli, Staphylococcus aureus, and MIC of the bacteria are found to be 5 µg/l and 10 µg/l, respectively. Despite having the biocompatible nature of ZnO, as-synthesized nanosheets have also shown cytotoxicity against two types of cancer cells, i.e. A549 and A375. Thus, ZnO nanosheets showed a nontoxic nature, which can be exploited as promising alternatives in different biomedical applications.


Assuntos
Antibacterianos , Antineoplásicos , Nanoestruturas , Óxido de Zinco , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Catálise , Antineoplásicos/farmacologia , Antineoplásicos/química , Nanoestruturas/química , Escherichia coli/efeitos dos fármacos , Ciprofloxacina/farmacologia , Ciprofloxacina/química , Staphylococcus aureus/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Linhagem Celular Tumoral , Processos Fotoquímicos , Fotólise
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...