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1.
Bioconjug Chem ; 31(3): 895-906, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32050064

RESUMO

Neuritogenesis, a complex process of the sprouting of neurites, plays a vital role in the structural and functional restoration of cerebral ischemia-injured neuronal tissue. Practically, there is no effective long-term treatment strategy for cerebral ischemia in clinical practice to date due to several limitations of conventional therapies, facilitating the urgency to develop new alternative therapeutic approaches. Herein, for the first time we report that pro-angiogenic nanomaterials, zinc oxide nanoflowers (ZONF), exhibit neuritogenic activity by elevating mRNA expression of different neurotrophins, following PI3K/Akt-MAPK/ERK signaling pathways. Further, ZONF administration to global cerebral ischemia-induced Fischer rats shows improved neurobehavior and enhanced synaptic plasticity of neurons via upregulation of Neurabin-2 and NT-3, revealing their neuroprotective activity. Altogether, this study offers the basis for exploitation of angio-neural cross talk of other pro-angiogenic nano/biomaterials for future advancement of alternative treatment strategies for cerebral ischemia, where neuritogenesis and neural repair are highly critical.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Nanoestruturas/química , Neuritos/efeitos dos fármacos , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Animais , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Linhagem Celular , Modelos Animais de Doenças , Neuritos/patologia , Fármacos Neuroprotetores/uso terapêutico , Ratos , Peixe-Zebra , Óxido de Zinco/uso terapêutico
2.
Cell Biochem Funct ; 35(4): 217-231, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28498520

RESUMO

Epidermal growth factor plays a major role in breast cancer cell proliferation, survival, and metastasis. Quercetin, a bioactive flavonoid, is shown to exhibit anticarcinogenic effects against various cancers including breast cancer. Hence, the present study was designed to evaluate the effects of gold nanoparticles-conjugated quercetin (AuNPs-Qu-5) in MCF-7 and MDA-MB-231 breast cancer cell lines. Borohydride reduced AuNPs were synthesized and conjugated with quercetin to yield AuNPs-Qu-5. Both were thoroughly characterized by several physicochemical techniques, and their cytotoxic effects were assessed by MTT assay. Apoptotic studies such as DAPI, AO/EtBr dual staining, and annexin V-FITC staining were performed. AuNPs and AuNPs-Qu-5 were spherical with crystalline nature, and the size of particles range from 3.0 to 4.5 nm. AuNPs-Qu-5 exhibited lower IC50 value compared to free Qu. There was a considerable increase in apoptotic population with increased nuclear condensation seen upon treatment with AuNPs-Qu-5. To delineate the molecular mechanism behind its apoptotic role, we analysed the proteins involved in apoptosis and epidermal growth factor receptor (EGFR)-mediated PI3K/Akt/GSK-3ß signalling by immunoblotting and immunocytochemistry. The pro-apoptotic proteins (Bax, Caspase-3) were found to be up regulated and anti-apoptotic protein (Bcl-2) was down regulated on treatment with AuNPs-Qu-5. Additionally, AuNPs-Qu-5 treatment inhibited the EGFR and its downstream signalling molecules PI3K/Akt/mTOR/GSK-3ß. In conclusion, administration of AuNPs-Qu-5 in breast cancer cell lines curtails cell proliferation through induction of apoptosis and also suppresses EGFR signalling. AuNPs-Qu-5 is more potent than free quercetin in causing cancer cell death, and hence, this could be a potential drug delivery system in breast cancer therapy.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Ouro/química , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quercetina , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Sistemas de Liberação de Medicamentos/métodos , Feminino , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Células MCF-7 , Nanopartículas Metálicas , Quercetina/química , Quercetina/farmacologia , Serina-Treonina Quinases TOR/metabolismo
3.
Bioorg Med Chem Lett ; 26(21): 5361-5368, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27546293

RESUMO

A new series of 2-imino-4-thiazolidinone derivatives (7a-7t) has been synthesised and screened for their cytotoxicity against three cancer cell lines (B16F10, A549, PANC-1) and normal cell line (CHO). Among the compounds tested, compounds 7k, 7m, 7n showed potent cytotoxicity against B16F10 cell line with IC50 between 3.4 and 7µM. Interestingly these three compounds are non toxic to non cancerous CHO cells and induced apoptosis in B16F10 cells observed by DNA damage analysis through PI/Hoechst double staining method. Compounds 7k and 7n induced G0/G1 cell cycle arrest while compound 7m induced G2/M cell cycle arrest in B16F10 cells which confirms that these compounds have role in cancer cell cycle regulation. Additionally, compound 7m showed generation of intracellular reactive oxygen species (ROS) in B16F10 cells that may contribute in the cell cycle arrest whereas compounds 7k and 7n show anti-cancer activity through independent of ROS formation. Induction of apoptosis, cell cycle arrest in B16F10 cells are found to be the anti-cancer mechanism of these three compounds. The results all together demonstrate the potent cytotoxic nature of these compounds in cancer cells could be considered as new class of chemotherapeutic agents in near future.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Tiazolidinas/síntese química , Tiazolidinas/farmacologia , Animais , Células CHO , Linhagem Celular Tumoral , Cricetinae , Cricetulus , Camundongos
5.
Nanomedicine ; 11(6): 1511-20, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25933692

RESUMO

Docetaxel (DTX) is an anticancer drug that is used alone and in combination with other drugs to treat tumours. However, it suffers from the drawback of non-specific cytotoxicity. To improve the therapeutic potential of DTX, we report the synthesis of cRGDfK peptide-conjugated succinoyl-TPGS (tocopheryl polyethylene glycol succinate) nanomicelles for targeted delivery of DTX. Among RGD (Arg-Gly-Asp) peptides, cRGDfK peptide shows specificity towards αvß3 integrin receptors that are most commonly over-expressed in tumour cells. To cRGDfK peptide, succinoylated TPGS was synthesised and conjugated to cRGDfK peptide using a carbodiimide reaction. Peptide-conjugated DTX loaded nanomicelles (PDNM) displayed small particle size with a narrow distribution, controlled drug release and high physicochemical stability. Cytotoxicity, cellular uptake, apoptosis and anti-angiogenic comparisons of unconjugated nanomicelles to PDNM in DU145 human prostate cancer cells and HUVECs (Human Umblical Vein Endothelial Cells) clearly revealed the importance of the cRGDfK peptide in enhancing the drug delivery performance of nanomicelles. FROM THE CLINICAL EDITOR: Common to many chemotherapeutic agents for cancer, systemic toxicity remains a big concern. In this article, the authors attempted to address this issue by conjugating RGD based peptides to Docetaxel, which would target integrins expressed on tumor cell surface. The experimental data revealed enhanced drug delivery.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Integrinas/metabolismo , Micelas , Nanoestruturas , Neovascularização Patológica , Peptídeos Cíclicos/química , Neoplasias da Próstata/tratamento farmacológico , Receptores de Superfície Celular/metabolismo , Taxoides/administração & dosagem , Vitamina E/análogos & derivados , Linhagem Celular Tumoral , Docetaxel , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Polietilenoglicóis/química , Neoplasias da Próstata/irrigação sanguínea , Neoplasias da Próstata/patologia , Vitamina E/química
6.
Biomed Mater ; 19(3)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38387050

RESUMO

Sodium nitroprusside (SNP), U.S approved drug has been used in clinical emergency as a hypertensive drug for more than a decade. It is well established for its various biomedical applications such as angiogenesis, wound healing, neurological disorders including anti-microbial applications etc. Apart from that, SNP have been considered as excellent biomedical materials for its use as anti-cancer agent because of its behavior as NO-donor. Recent reports suggest that incorporation of metals in SNP/encapsulation of SNP in metal nanoparticles (metal nitroprusside analogues) shows better therapeutic anti-cancer activity. Although there are numerous reports available regarding the biological applications of SNP and metal-based SNP analogue nanoparticles, unfortunately there is not a single comprehensive review which highlights the anti-cancer activity of SNP and its derivative metal analogues in detail along with the future perspective. To this end, the present review article focuses the recent development of anti-cancer activity of SNP and metal-based SNP analogues, their plausible mechanism of action, current status. Furthermore, the future perspectives and challenges of these biomedical materials are also discussed. Overall, this review article represents a new perspective in the area of cancer nanomedicine that will attract a wider spectrum of scientific community.


Assuntos
Fármacos Cardiovasculares , Neoplasias , Nitroprussiato/metabolismo , Nitroprussiato/farmacologia , Nitroprussiato/uso terapêutico , Metais , Neoplasias/tratamento farmacológico
7.
Nanoscale ; 16(28): 13580-13596, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-38953490

RESUMO

Melanoma is the most invasive and lethal form of skin cancer that arises from the malignant transformation of specialized pigment-producing cell melanocytes. Nanomedicine represents an important prospect to mitigate the difficulties and provide significant benefits to cure melanoma. In the present study, we investigated in vitro and in vivo therapeutic efficacies of copper nitroprusside analogue nanoparticles (abbreviated as CuNPANP) towards melanoma. Initially, in vitro anti-cancer activities of CuNPANP towards melanoma cells (B16F10) were evaluated by several experiments such as [methyl-3H]-thymidine incorporation assay, cell cycle and apoptosis assays using FACS analysis, ROS generation using DCFDA, DHE and DAF2A reagents, internalization of nanoparticles through ICP-OES analysis, co-localization of the nanoparticles using confocal microscopy, JC-1 staining to investigate the mitochondrial membrane potential (MMP) and immunofluorescence studies to analyze the expressions of cytochrome-c, Ki-67, E-cadherin as well as phalloidin staining to analyze the cytoskeletal integrity. Further, the in vivo therapeutic effectiveness of the nanoparticles was established towards malignant melanoma by inoculating B16F10 cells in the dorsal right abdomen of C57BL/6J mice. The intraperitoneal administration of CuNPANP inhibited tumor growth and increased the survivability of melanoma mice. The in vivo immunofluorescence studies (Ki-67, CD-31, and E-cadherin) and TUNEL assay further support the anti-cancer and apoptosis-inducing potential of CuNPANP, respectively. Finally, various signaling pathways and molecular mechanisms involved in anti-cancer activities were further evaluated by Western blot analysis. The results altogether indicated the potential use of copper-based nanomedicines for the treatment of malignant melanoma.


Assuntos
Apoptose , Cobre , Melanoma Experimental , Camundongos Endogâmicos C57BL , Nitroprussiato , Animais , Camundongos , Linhagem Celular Tumoral , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Melanoma Experimental/metabolismo , Apoptose/efeitos dos fármacos , Cobre/química , Cobre/farmacologia , Nitroprussiato/farmacologia , Nitroprussiato/química , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Melanoma/tratamento farmacológico , Melanoma/patologia , Melanoma/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacologia , Nanopartículas/química , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/metabolismo , Proliferação de Células/efeitos dos fármacos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico
8.
Biomater Adv ; 160: 213832, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38547763

RESUMO

Triple negative breast cancer (TNBC) is an aggressive form of tumor, more prevalent in younger women resulting in poor survival rate (2nd in cancer deaths) because of its asymptomatic existence. The most popular and convenient approach for the treatment of TNBC is chemotherapy which is associated with several limitations. Considering the importance of nanotechnology in health care system, in the present manuscript, we have designed and developed a simple, efficient, cost effective, and ecofriendly method for the synthesis of copper nitroprusside analogue nanoparticles (Cu[Fe(CN)5NO] which is abbreviated as CuNPANP that may be the potential anti-cancer nanomedicine for the treatment of TNBC. Copper (present in CuNPANP) is used because of its affordability, nutritional value and various biomedical applications. The CuNPANP are thoroughly characterized using several analytical techniques. The in vitro cell viability (in normal cells) and the ex vivo hemolysis assay reveal the biocompatible nature of CuNPANP. The anti-cancer activity of the CuNPANP is established in TNBC cells (MDA-MB-231 and 4T1) through several in vitro assays along with plausible mechanisms. The intraperitoneal administration of CuNPANP in orthotopic breast tumor model by transplanting 4T1 cells into the mammary fat pad of BALB/c mouse significantly inhibits the growth of breast carcinoma as well as increases the survival time of tumor-bearing mice. These results altogether potentiate the anti-cancer efficacy of CuNPANP as a smart therapeutic nanomedicine for treating TNBC in near future after bio-safety evaluation in large animals.


Assuntos
Cobre , Espécies Reativas de Oxigênio , Neoplasias de Mama Triplo Negativas , Animais , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Feminino , Camundongos , Cobre/química , Cobre/farmacologia , Cobre/administração & dosagem , Humanos , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Camundongos Endogâmicos BALB C , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/química , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças
9.
ACS Appl Bio Mater ; 7(7): 4389-4405, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38848346

RESUMO

Critical limb ischemia (CLI) refers to a severe condition resulting from gradual obstruction in the supply of blood, oxygen, and nutrients to the limbs. The most promising clinical solution to CLI is therapeutic angiogenesis. This study explored the potency of pro-angiogenic terbium hydroxide nanorods (THNR) for treatment of CLI, with a major focus on their impact on ischemia-induced maladaptive alterations in endothelial cells as well as on vascularization in ischemic limbs. This study demonstrated that, in hypoxia-exposed endothelial cells, THNR improve survival and promote proliferation, migration, restoration of nitric oxide production, and regulation of vascular permeability. Based on molecular studies, these attributes of THNR can be traced to the stimulation of PI3K/AKT/eNOS signaling pathways. Besides, Wnt/GSK-3ß/ß-catenin signaling pathways may also play a role in the therapeutic actions of THNR. Furthermore, in the murine model of CLI, THNR administration can integrally re-establish blood perfusion with concomitant reduction of muscle damage and inflammation. Additionally, improvement of locomotor activities and motor coordination in ischemic limbs in THNR treated mice is also evident. Overall, the study demonstrates that THNR have the potential to be developed as an efficacious and cost-effective alternative clinical therapy for CLI, using a nanomedicine approach.


Assuntos
Isquemia , Nanotubos , Animais , Nanotubos/química , Camundongos , Isquemia/tratamento farmacológico , Isquemia/patologia , Isquemia/metabolismo , Humanos , Hidróxidos/química , Hidróxidos/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Masculino , Teste de Materiais , Proliferação de Células/efeitos dos fármacos , Tamanho da Partícula , Camundongos Endogâmicos C57BL , Células Endoteliais da Veia Umbilical Humana , Membro Posterior/patologia
10.
Nanomedicine (Lond) ; 18(3): 191-196, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36896894

RESUMO

Tweetable abstract Nanotechnology and its role in hair growth by enhancing drug delivery for the management of alopecia #nanotechnology #hair #drug_delivery.


Assuntos
Nanomedicina , Nanopartículas , Humanos , Nanotecnologia , Cabelo , Alopecia/tratamento farmacológico , Sistemas de Liberação de Medicamentos
11.
Biomater Adv ; 153: 213531, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37429046

RESUMO

Myocardial hypoxia reperfusion (H/R) injury is the paradoxical exacerbation of myocardial damage, caused by the sudden restoration of blood flow to hypoxia affected myocardium. It is a critical contributor of acute myocardial infarction, which can lead to cardiac failure. Despite the current pharmacological advancements, clinical translation of cardioprotective therapies have proven challenging. As a result, researchers are looking for alternative approaches to counter the disease. In this regard, nanotechnology, with its versatile applications in biology and medicine, can confer broad prospects for treatment of myocardial H/R injury. Herein, we attempted to explore whether a well-established pro-angiogenic nanoparticle, terbium hydroxide nanorods (THNR) can ameliorate myocardial H/R injury. For this study, in vitro H/R-injury model was established in rat cardiomyocytes (H9c2 cells). Our investigations demonstrated that THNR enhance cardiomyocyte survival against H/R-induced cell death. This pro-survival effect of THNR is associated with reduction of oxidative stress, lipid peroxidation, calcium overload, restoration of cytoskeletal integrity and mitochondrial membrane potential as well as augmentation of cellular anti-oxidant enzymes such as glutathione-s-transferase (GST) and superoxide dismutase (SOD) to counter H/R injury. Molecular analysis revealed that the above observations are traceable to the predominant activation of PI3K-AKT-mTOR and ERK-MEK signalling pathways by THNR. Concurrently, THNR also exhibit apoptosis inhibitory effects mainly by suppression of pro-apoptotic proteins like Cytochrome C, Caspase 3, Bax and p53 with simultaneous restoration of anti-apoptotic protein, Bcl-2 and Survivin. Thus, considering the above attributes, we firmly believe that THNR have the potential to be developed as an alternative approach for amelioration of H/R injury in cardiomyocytes.


Assuntos
Traumatismo por Reperfusão Miocárdica , Nanotubos , Animais , Ratos , Miócitos Cardíacos/metabolismo , Térbio/metabolismo , Térbio/farmacologia , Térbio/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Linhagem Celular , Hipóxia/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo
12.
Nanoscale ; 15(23): 10017-10032, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37232231

RESUMO

The advancement of nanotechnology has led to the experimental development of cancer therapeutics, which may overcome the shortcomings of commercially available drugs and facilitate improved clinical outcomes. Recently, several metal nanoparticles, especially silver, have been evaluated by scientists globally as useful chemotherapeutic agents due to their multi-functionality and well-recognized biological activity. Herein, we developed silver nitroprusside nanoparticles (abbreviated as AgNNPs) with slight modifications in the reaction conditions and demonstrated their application for breast cancer therapy using in vitro assays and in vivo experiments in a mouse model. Initially, the modified AgNNPs were thoroughly characterized using several analytical techniques. AgNNPs were found to be biocompatible according to in vitro experiments in normal cell lines (HEK-293 and EA.hy926), which was further validated by a hemolysis assay (ex vivo experiment) using mouse red blood cells. In contrast, the cell viability assay using the MTT reagent showed the cytotoxic nature of the AgNNPs against several cancer cell lines (MDA-MB-231, 4T1, B16F10, and PANC-1). Their detailed anticancer activity was investigated using 4T1 (mouse specific) and MDA-MB-231 (human specific) cells through various in vitro assays. The nanoparticles inhibited the formation of blood vessels in the chick embryo model, highlighting their anti-angiogenic behavior. Furthermore, the administration of AgNNPs significantly inhibited orthotopic breast tumor growth (4T1; BALB/c mice) and increased the survivability of the tumor-bearing mice. Also, we demonstrated the plausible molecular mechanisms for the anti-cancer activity of AgNNPs through various in vitro assays and in vivo experiments. Overall, the results support that AgNNPs can be used as an alternative generalized nanomedicine for the treatment of breast and other cancers after proper biosafety evaluation in near future.


Assuntos
Antineoplásicos , Neoplasias da Mama , Nanopartículas Metálicas , Embrião de Galinha , Humanos , Animais , Camundongos , Feminino , Neoplasias da Mama/patologia , Nitroprussiato/farmacologia , Nitroprussiato/uso terapêutico , Prata/farmacologia , Linhagem Celular Tumoral , Células HEK293 , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Apoptose , Camundongos Endogâmicos BALB C
13.
Nanotoxicology ; 17(10): 604-627, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38105710

RESUMO

Recently, we have demonstrated casein manganese oxide nanoparticles (CMnNP) that exhibit pro-angiogenic property established through different in vitro and in vivo experiments. The CMnNP was explored for therapeutic angiogenesis for treatment of wounds and recovery of hindlimb ischemia in pre-clinical mouse prototypical. It is well known that to translate any therapeutic nanoparticle for future clinical applications, their biosafety evaluation in small and large animals is essential. Herein, in the current study, the biosafety and bioavailability of the CMnNP have been explored by a systematic toxicity profiling study in C57BL/6J mice model. Initially, the in vitro cytotoxic effects of CMnNP were validated in RAW 264.7 cells. Later, the CMnNP was administered intraperitoneally with different doses (50, 300, and 2000 mg/kg b.wt./day) at different time points of exposure (acute: 2 weeks, sub-chronic: 4 weeks as well as chronic exposure: 8 and 20 weeks) with reference to the maximum tolerable dose (MTD) of CMnNP as per the OECD guidelines. The blood hematological and serum biochemical parameters of CMnNP treatment groups indicate negligible changes similar to untreated group. The histopathological examination of CMnNP-treated vital organs (lung, spleen, liver, brain, kidney, and heart) illustrates no major changes even at higher doses. Further, the biodistribution and excretion study depicts normal clearance of CMnNP. Additionally, the serum cytokine levels were normal in the therapeutic dose of CMnNP. The results altogether indicate that the non-toxic nature of CMnNP makes them useful as future therapeutic angiogenic agent for the treatment of various diseases where angiogenesis plays an important role.


Assuntos
Caseínas , Compostos de Manganês , Nanopartículas , Óxidos , Camundongos , Animais , Caseínas/toxicidade , Distribuição Tecidual , Camundongos Endogâmicos C57BL , Nanopartículas/toxicidade
14.
NanoImpact ; 31: 100479, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37572937

RESUMO

Our earlier reports established that zinc oxide nanoflowers (ZONF) show significant pro-angiogenic properties, where reactive oxygen species, nitric oxide and MAPK-AKT-eNOS cell signaling axis play an essential task. Considering the significance of angiogenesis in healthcare, our research group has recently demonstrated the in vivo therapeutic application of ZONF (10 mg/kg b.w.) for treating peripheral artery disease. Moreover, based on the angio-neural crosstalk between vascular and neuronal systems, we have further demonstrated the neuritogenic and neuroprotective characteristics of pro-angiogenic nanoflowers (10 mg/kg b.w.) for the treatment of cerebral ischemia. However, it is crucial for a therapeutic material to be non-toxic for its practical clinical applications and therefore assessment of its in vivo toxicity and adverse effect is highly important. Herein, for the first time, we investigate a detailed nanotoxicology of therapeutically active ZONF in Swiss albino mice to evaluate their safety profile and comprehend their aspects for future clinical applications. The maximum tolerated dose (MTD) of ZONF was found to be 512.5 mg/kg b.w. which was employed for acute exposure (2 weeks), showing slight toxicity. However, sub-chronic (4 weeks) and long term chronic (8-12 weeks) studies of nanoflowers exhibited their non-toxic nature particularly at lower therapeutic doses (1-10 mg/kg b.w.). Additionally, in depth genotoxicity study revealed that lower therapeutic dose of ZONF (10 mg/kg b.w.) did not exhibit significant toxicity even in genetic level. Overall, the present nanotoxicology of ZONF suggests their high biocompatible nature at therapeutic dose, offering the basis of their future clinical applications in ischemic and other vascular diseases.


Assuntos
Óxido de Zinco , Camundongos , Animais , Óxido de Zinco/toxicidade , Espécies Reativas de Oxigênio
15.
Nanotechnology ; 23(45): 455103, 2012 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-23064012

RESUMO

The biological approach to synthesis of AuNPs is eco-friendly and an ideal method to develop environmentally sustainable nanoparticles alternative to existing methods. We have developed a simple, fast, clean, efficient, low-cost and eco-friendly single-step green chemistry approach for the synthesis of biocompatible gold nanoparticles (AuNPs) from chloroauric acid (HAuCl(4)) using a water extract of Eclipta Alba leaves at room temperature. The AuNPs using Eclipta extract have been formed in very short time, even in less than 10 min. The as-synthesized AuNPs were thoroughly characterized by several physico-chemical techniques. The in vitro stability of as-synthesized AuNPs was studied in different buffer solutions. A plausible mechanism for the synthesis of AuNPs by Eclipta extract has been discussed. The biocompatibility of AuNPs was observed by in vitro cell culture assays. Finally, we have designed and developed a AuNPs-based drug delivery system (DDS) (Au-DOX) containing doxorubicin (DOX), a FDA approved anticancer drug. Administration of this DDS to breast cancer cells (MCF-7 and MDA-MB-231) shows significant inhibition of breast cancer cell proliferation compared to pristine doxorubicin. Therefore we strongly believe that the use of Eclipta Alba offers large-scale production of biocompatible AuNPs that can be used as a delivery vehicle for the treatment of cancer diseases.


Assuntos
Portadores de Fármacos/química , Eclipta/química , Ouro/química , Química Verde/métodos , Nanopartículas Metálicas/química , Extratos Vegetais/química , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cloretos/química , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Portadores de Fármacos/síntese química , Feminino , Compostos de Ouro/química , Química Verde/economia , Humanos , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química
16.
Nano Lett ; 11(11): 4932-8, 2011 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-21967244

RESUMO

The exact mechanism of angiogenesis by europium hydroxide nanorods was unclear. In this study we have showed that formation of reactive oxygen species (H(2)O(2) and O(2)·-) is involved in redox signaling pathways during angiogenesis, important for cardiovascular and ischemic diseases. Here we used single-walled carbon nanotube sensor array to measure the single-molecule efflux of H(2)O(2) and a HPLC method for the determination of O(2)·- from endothelial cells in response to proangiogenic factors. Additionally, reactive oxygen species-mediated angiogenesis using inorganic nanorods was observed in transgenic (fli1a:EGFP) zebrafish embryos.


Assuntos
Células Endoteliais/efeitos dos fármacos , Células Endoteliais/fisiologia , Compostos Inorgânicos/farmacologia , Nanopartículas/administração & dosagem , Neovascularização Fisiológica/efeitos dos fármacos , Neovascularização Fisiológica/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Células Cultivadas , Humanos
17.
Biomater Adv ; 137: 212819, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35929256

RESUMO

Nanotechnology has immensely advanced the field of cancer diagnostics and treatment by introducing potential delivery vehicles as carriers for drugs or therapeutic agents. In due course, mesoporous silica nanoparticles (MSNs) have emerged as excellent vehicles for delivering drugs, biomolecules, and biomaterials, attributed to their solid framework and porosity providing a higher surface area for decorating with various functional ligands. Recently, the metal tin (Sn) has gained huge importance in cancer research owing to its excellent cytotoxicity and ability to kill cancer cells. In the present work, we synthesized MSNs, conjugated them with organotin compounds, and characterized them using various physicochemical techniques. Subsequently, the biological evaluation of MSN (S1), MSN-MP (S2) and tin-conjugated MSNs (S3: MSN-MP-SnPh3) (MP = 3-mercaptopropyltriethoxysilane) revealed that these nanoconjugates induced cytotoxicity, necrosis, and apoptosis in MCF-7 cells. Moreover, these nanoconjugates exhibited anti-angiogenic properties as demonstrated in the chick embryo model. The increase of reactive oxygen species (ROS) was found as a one of the plausible mechanisms underlying cancer cell cytotoxicity induced by these nanoconjugates, encouraging their application for the treatment of cancer. The tin-conjugated MSNs demonstrated less toxicity to normal cells compared to cancer cells. Furthermore, the genotoxicity studies revealed the clastogenic and aneugenic effects of these nanoconjugates in CHO cells mostly at high concentrations. These interesting observations are behind the idea of developing tin-conjugated MSNs as prospective candidates for anticancer therapy.


Assuntos
Antineoplásicos , Dióxido de Silício , Estanho , Animais , Embrião de Galinha , Cricetinae , Humanos , Antineoplásicos/farmacologia , Sobrevivência Celular , Cricetulus , Portadores de Fármacos/química , Nanoconjugados , Dióxido de Silício/química , Estanho/farmacologia
18.
Nanoscale ; 13(39): 16405-16426, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34586121

RESUMO

Nanotechnology is the most promising technology to evolve in the last decade. Recent research has shown that transition metal nanoparticles especially manganese (Mn)-based nanoparticles have great potential for various biomedical applications due to their unique fundamental properties. Therefore, globally, scientists are concentrating on the development of various new manganese-based nanoparticles (size and shape dependent) due to their indispensable utilities. Although numerous reports are available regarding the use of manganese nanoparticles, there is no comprehensive review highlighting the recent development of manganese-based nanomaterials and their potential applications in the area of biomedical sciences. The present review article provides an overall survey on the recent advancement of manganese nanomaterials in biomedical nanotechnology and other fields. Further, the future perspectives and challenges are also discussed to explore the wider application of manganese nanoparticles in the near future. Overall, this review presents a fundamental understanding and the role of manganese in various fields, which will attract a wider spectrum of the scientific community.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Nanoestruturas , Íons , Manganês , Nanopartículas Metálicas/toxicidade , Nanotecnologia
19.
Cancers (Basel) ; 13(23)2021 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-34885224

RESUMO

In the current communication, a simple, environmentally compatible, non-toxic green chemistry process is used for the development of silver nanoparticles (AgZE) by the reaction between silver nitrate (AgNO3) and the ethanolic leaf extract of Zinnia elegans (ZE). The optimization of AgZE is carried out using a series of experiments. Various physico-chemical techniques are utilized to characterize the nanomaterials. The cell viability assay of AgZE in normal cells (CHO, HEK-293T, EA.hy926, and H9c2) shows their biocompatible nature, which is supported by hemolytic assay using mouse RBC. Interestingly, the nanoparticles exhibited cytotoxicity towards different cancer cell lines (U-87, MCF-7, HeLa, PANC-1 and B16F10). The detailed anticancer activity of AgZE on human glioblastoma cell line (U-87) is exhibited through various in vitro assays. In vivo the AgZE illustrates anticancer activity by inhibiting blood vessel formation through CAM assay. Furthermore, the AgZE nanoparticles when intraperitoneally injected in C57BL6/J mice (with and without tumor) exhibit fluorescence properties in the NIR region (excitation: 710 nm, emission: 820 nm) evidenced by bioimaging studies. The AgZE biodistribution through ICPOES analysis illustrates the presence of silver in different vital organs. Considering all the results, AgZE could be useful as a potential cancer therapeutic agent, as well as an NIR based non-invasive imaging tool in near future.

20.
ACS Appl Mater Interfaces ; 13(9): 10689-10704, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33621045

RESUMO

There have been reports of different types of wound dressings for various functions and purposes. Cotton being one of the most widely used wound dressing material due to its non-toxic, biodegradable, and other properties is used for fabrication as well as in the form of scaffolds for faster and effective wound closure. Our research team has already demonstrated the role of silver nitroprusside nanoparticles (SNPNPs) for wound healing and antibacterial activity. In the current study, we have developed cotton fabric impregnated with SNPNPs (SNPCFs) which remain photo inert and displayed long-term antimicrobial activity due to the surface modification with the silver nitroprusside complex. These SNPCFs were characterized by various analytical techniques (XRD, FTIR, UV spectroscopy, TGA, TEM, FESEM, EDAX, ICP-OES). The fabricated cotton dressings with nanoparticles showed an improved water contact angle (113-130°) than that of bare cotton gauze (60°) and exhibited more antibacterial property in case of both Gram-negative bacteria (Klebsiella aerogenes and Escherichia coli) and Gram-positive bacteria (Pseudomonas aeruginosa and Bacillus subtilis) even after several washings. The biocompatible nature of SNPCFs was assessed by in vivo chorioallantoic membrane assay that showed no obstruction in the formation of blood vessels. The SNPCFs exhibited better wound healing activity compared to the bare cotton and AgCFs as observed in the C57BL6/J mouse. The histopathological investigation reveals increase in re-epithelialization and deposition of connective tissue. The macrophage (M2) counts in SNPCF-treated skin tissues were supportive of more wound healing activity than mice treated with cotton fabric impregnated with chemically synthesized silver nanoparticles. Based on biodistribution analysis using ICP-OES, the data illustrated that a significant amount of silver is absorbed in the skin tissues of mice as compared to the blood and kidney. Furthermore, the absence of silver from the vital organs (heart, liver, and kidney) corroborates our hypothesis that the SNPCFs can act excellently in treating wounds when topically applied over skin. Thereafter, all these results highlight a strong possibility that SNPCFs exemplify the potential as a new antimicrobial and wound healing agent in future times.


Assuntos
Antibacterianos/uso terapêutico , Bandagens , Nanopartículas Metálicas/uso terapêutico , Nitroprussiato/uso terapêutico , Compostos de Prata/uso terapêutico , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/química , Antibacterianos/farmacocinética , Bactérias/efeitos dos fármacos , Fibra de Algodão , Feminino , Gossypium/química , Nanopartículas Metálicas/química , Camundongos , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana , Nitroprussiato/química , Nitroprussiato/farmacocinética , Células RAW 264.7 , Compostos de Prata/química , Compostos de Prata/farmacocinética
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