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1.
Inorg Chem ; 61(37): 14568-14581, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-35914234

RESUMO

Defect engineering, such as modification of oxygen vacancy density, has been considered as an effective approach to tailor the catalytic performance on transition-metal oxide nanostructured surfaces. The role of oxygen vacancies (OV) on the surface of the as-prepared, zinnia-shaped morphology of CuO nanostructures and their marigold forms on calcination at 800 °C has been investigated through the study of model catalytic reactions of reduction of 4-nitrophenol and aerobic oxidation of benzyl alcohol. The OV on the surfaces of different morphologies of CuO have been identified and quantified through Rietveld analysis and HRTEM, EPR, and XPS studies. The structure-activity relationships between surface oxygen vacancies (OV) and catalytic performance have been systematically investigated. The enhanced catalytic performance of the cubic CuO nanostructures compared to their as-prepared forms has been attributed to the formation of surface oxygen species on the reactive and dominant (110) surface that has low oxygen vacancy formation energy. The mechanistic role of surface oxygen species in the studied reactions has been quantitatively correlated with the catalytic activity of the different morphological forms of the CuO nanostructures.

2.
Langmuir ; 33(31): 7649-7659, 2017 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-28701038

RESUMO

The therapeutic index of poorly water-soluble drugs is often hampered due to poor pharmacokinetics, reduced blood retention, and lack of effective drug concentrations in the tumor region. In order to overcome these issues, drugs are often delivered by use of delivery vehicles to provide an enhanced therapeutic index. Gold nanoparticles synthesized in micellar networks of amphiphilic block copolymer (AuNM) provide an efficient nanocarrier for tissue- and site-specific drug delivery owing to their low cytotoxicity and immunogenicity. AuNM is formed by exploiting the properties of both inorganic Au material and an amphiphilic polymer of poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (PEG-PPG-PEG). We further functionalized AuNM with the FDA-approved dual tyrosine kinase inhibitor ZD6474 and studied the physicochemical properties of the conjugate ZD6474-AuNM. Both AuNM and ZD6474-AuNM, with a diameter of ∼70 nm, were very stable at physiological pH. Conversely, at an acidic pH of 5.2, a slow sustained-release profile of ZD6474 was evident from AuNM, which could provide a method of facilitating release of the drug in an acidic tumor environment. In vitro, in triple-negative breast cancer cells, ZD6474-AuNM inhibited tumor cell proliferation, migration, and invasion and induced apoptosis. There was no detectable lysis of red blood cells observed when they were treated with AuNM and ZD6474-AuNM, confirming hemocompatibility. To reinforce the possibility of AuNM serving as a delivery vehicle, AuNM was conjugated with the IR680 dye for tracking, and this conjugate was systemically delivered in female nude mice bearing MDA-MB-231 human breast cancer xenografts. Fluorescence signal was retained in the tumor region in a temporal manner as compared to other organs, indicating passive retention of AuNM in the tumor locale. Moreover, delivery of ZD6474-AuNM in nude mice bearing MDA-MB-231 xenografts led to decreased tumor size as compared to the control group. The promising safety, targeting, and therapeutic results of systemic delivery of ZD6474 by AuNM provide an attractive alternative method for treating patients with metastatic breast cancer.


Assuntos
Nanopartículas Metálicas , Animais , Neoplasias da Mama , Linhagem Celular Tumoral , Feminino , Ouro , Humanos , Camundongos , Camundongos Nus , Micelas , Piperidinas , Polietilenoglicóis , Inibidores de Proteínas Quinases , Proteínas Tirosina Quinases , Quinazolinas
3.
Mol Pharm ; 12(12): 4214-25, 2015 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-26505213

RESUMO

Akt overexpression in cancer causes resistance to traditional chemotherapeutics. Silencing Akt through siRNA provides new therapeutic options; however, poor in vivo siRNA pharmacokinetics impede translation. We demonstrate that acidic milieu-sensitive multilamellar gold niosomes (Nio-Au) permit targeted delivery of both Akt-siRNA and thymoquinone (TQ) in tamoxifen-resistant and Akt-overexpressing MCF7 breast cancer cells. Octadecylamine groups of functionalized gold nanoparticles impart cationic attribute to niosomes, stabilized through polyethylene glycol. TQ's aqueous insolubility renders its encapsulation within hydrophobic core, and negatively charged siRNA binds in hydrophilic region of cationic niosomes. These niosomes were exploited to effectively knockdown Akt, thereby sensitizing cells to TQ. Immunoblot studies revealed enhanced apoptosis by inducing p53 and inhibiting MDM2 expression, which was consistent with in vivo xenograft studies. This innovative strategy, using Nio-Au to simultaneously deliver siRNA (devoid of any chemical modification) and therapeutic drug, provides an efficacious approach for treating therapy-resistant cancers with significant translational potential.


Assuntos
Benzoquinonas/farmacologia , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ouro/administração & dosagem , Nanopartículas/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/genética , Apoptose/efeitos dos fármacos , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Feminino , Humanos , Células MCF-7 , Tamoxifeno/farmacologia
4.
Sci Technol Adv Mater ; 13(4): 045008, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27877508

RESUMO

Water-soluble carbon dots (C-dots) were prepared through microwave-assisted pyrolysis of an aqueous solution of dextrin in the presence of sulfuric acid. The C-dots produced showed multicolor luminescence in the entire visible range, without adding any surface-passivating agent. X-ray diffraction and Fourier transform infrared spectroscopy studies revealed the graphitic nature of the carbon and the presence of hydrophilic groups on the surface, respectively. The formation of uniformly distributed C-dots and their luminescent properties were, respectively, revealed from transmission electron microscopy and confocal laser scanning microscopy. The biocompatible nature of C-dots was confirmed by a cytotoxicity assay on MDA-MB-468 cells and their cellular uptake was assessed through a localization study.

5.
Curr Pharm Biotechnol ; 23(9): 1132-1141, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34387162

RESUMO

BACKGROUND: Pinus belongs to the family Pinaceae, represented by several species across the globe. Various parts of the plant including needles are rich in biologically active compounds, such as thunbergol, 3-carene, cembrene, α-pinene, quercetin, xanthone. Of all the alkaloids, the piperidine group is one of the important component and holds considerable medicinal importance. METHODS: The group of alkaloids was initially identified from the genus Piper through which a large variety of piperidine molecules have been extracted. The planar structure of this heterocyclic nucleus enables acetamide groups to be added at various ring configurations. RESULTS: Piperidines have gained considerable importance. The broad range of its therapeutic application has paved a way for researchers to implant the nucleus from time to time in diversified pharmacophores and establish new profile. DISCUSSION: Biological functions of piperidine metabolites have been mostly examined on a limited scale, and that most of the findings are preliminary. We have tried to present various clinical applications of piperidine alkaloids in this study that researchers have already attempted to demystify with time. CONCLUSION: We have also illustrated different types of piperidine structures and their sources in different members of the family Pinaceae with special emphasis on Pinus. Given the importance of the piperidine nucleus, the study will enable the researchers to produce scaffolds of highest therapeutic efficacy.


Assuntos
Alcaloides , Pinus , Alcaloides/química , Alcaloides/farmacologia , Pinus/química , Piperidinas/química , Piperidinas/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia
6.
RSC Adv ; 8(74): 42361-42373, 2018 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-35558411

RESUMO

Nitrogen and sulfur co-doped carbon dots (NSCDs) synthesized through one-pot microwave-assisted pyrolysis of tartaric acid and thioacetamide have been used as a fluorescent probe for the sensitive and selective detection of clinically important organic aldehyde cinnamaldehyde. The as-prepared NSCDs displayed blue fluorescence (∼12% quantum yield), excellent aqueous solubility along with pH and excitation wavelength dependent emission behavior. In comparison to other aldehydes (formaldehyde, acetaldehyde, propionaldehyde, butyraldehyde, valeraldehyde, hexanal, crotonaldehyde and benzaldehyde) the fluorescence intensity of NSCDs was significantly quenched in the presence of cinnamaldehyde and the reduced intensity was linearly proportional to the concentration of cinnamaldehyde in the range of 0-15 mM with a detection limit of 99.0 µM. The fluorescence quenching of NSCDs was mainly attributed to the photo-excited electron transfer between NSCDs and aldehydes which was confirmed by measuring the life-time through time-resolved luminescence spectroscopy, energy levels of NSCDs through cyclic voltammetry (CV) and energy levels of aldehydes by density functional theory (DFT) based analyses. MTT assay of the NSCDs also proved their good biocompatibility and low toxicity towards human fibroblast cells thereby validating their suitability as a biologically relevant fluorescent probe for sensing cinnamaldehyde.

7.
J Phys Chem B ; 121(51): 11437-11448, 2017 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-29202580

RESUMO

The influence of different morphologies of nanostructures on amyloid fibrillation has been investigated by monitoring the fibrillation of human serum albumin (HSA) in the presence of rod-, sphere-, flower-, and star-shaped copper oxide (CuO) nanostructures. The different morphologies of CuO have been synthesized from an aqueous solution-based precipitation method using various organic acids, viz., acetic acid, citric acid, and tartaric acid. The fibrillation process of HSA has been examined using various biophysical techniques, e.g., Thioflavin T fluorescence, Congo red binding studies through UV spectroscopy, circular dichroism spectroscopy, and fluorescence microscopy. The monolayer protein coverage on the CuO nanostructures has been established through DLS studies, and the well-fitted Langmuir isotherm model has been used to interpret the differential adsorption behavior of HSA molecules on the CuO nanostructures. The nanostar-shaped CuO, by virtue of their higher specific surface area (94.45 m2 g-1), presence of high indexed facets {211} and high positive surface charge potential (+16.2 mV at pH 7.0) was found to show the highest adsorption of the HSA monomers and thus was more competent to inhibit the formation of HSA fibrils compared to the other nanostructures of CuO.


Assuntos
Cobre/química , Nanoestruturas/química , Albumina Sérica Humana/química , Adsorção , Benzotiazóis , Corantes Fluorescentes/química , Humanos , Microscopia de Fluorescência , Tamanho da Partícula , Propriedades de Superfície , Tiazóis/química
8.
Mater Sci Eng C Mater Biol Appl ; 60: 84-91, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26706510

RESUMO

The present work reports the synthesis of biocompatible zirconium phosphate (ZP) nanoparticles as nanocarrier for drug delivery application. The ZP nanoparticles were synthesized via a simple sonochemical method in the presence of cetyltrimethylammonium bromide and their efficacy for the delivery of drugs has been tested through various in-vitro experiments. The particle size and BET surface area of the nanoparticles were found to be ~48 nm and 206.51 m(2)/g respectively. The conventional MTT assay and cellular localization studies of the particles, performed on MDA-MB-231 cell lines, demonstrate their excellent biocompatibility and cellular internalization behavior. The loading of curcumin, an antitumor drug, onto the ZP nanoparticles shows the rapid drug uptake ability of the particles, while the drug release study, performed at two different pH values (at 7.4 and 5) depicts pH sensitive release-profile. The MTT assay and cellular localization studies revealed higher cellular inhibition and better bioavailability of the nanoformulated curcumin compared to free curcumin.


Assuntos
Materiais Biocompatíveis/química , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Zircônio/química , Linhagem Celular Tumoral , Humanos , Concentração de Íons de Hidrogênio
9.
Sci Rep ; 5: 11760, 2015 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-26145450

RESUMO

Low pH in the tumor micromilieu is a recognized pathological feature of cancer. This attribute of cancerous cells has been targeted herein for the controlled release of chemotherapeutics at the tumour site, while sparing healthy tissues. To this end, pH-sensitive, hollow ZnO-nanocarriers loaded with paclitaxel were synthesized and their efficacy studied in breast cancer in vitro and in vivo. The nanocarriers were surface functionalized with folate using click-chemistry to improve targeted uptake by the malignant cells that over-express folate-receptors. The nanocarriers released ~75% of the paclitaxel payload within six hours in acidic pH, which was accompanied by switching of fluorescence from blue to green and a 10-fold increase in the fluorescence intensity. The fluorescence-switching phenomenon is due to structural collapse of the nanocarriers in the endolysosome. Energy dispersion X-ray mapping and whole animal fluorescent imaging studies were carried out to show that combined pH and folate-receptor targeting reduces off-target accumulation of the nanocarriers. Further, a dual cell-specific and pH-sensitive nanocarrier greatly improved the efficacy of paclitaxel to regress subcutaneous tumors in vivo. These nanocarriers could improve chemotherapy tolerance and increase anti-tumor efficacy, while also providing a novel diagnostic read-out through fluorescent switching that is proportional to drug release in malignant tissues.


Assuntos
Antineoplásicos Fitogênicos/química , Portadores de Fármacos/química , Nanopartículas Metálicas/química , Paclitaxel/química , Óxido de Zinco/química , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/toxicidade , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Progressão da Doença , Feminino , Humanos , Concentração de Íons de Hidrogênio , Nanopartículas Metálicas/ultraestrutura , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Microscopia de Fluorescência , Paclitaxel/administração & dosagem , Paclitaxel/toxicidade , Transplante Heterólogo
10.
J Mater Chem B ; 3(1): 90-101, 2015 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-32261929

RESUMO

Single drug therapies for cancer are often suboptimal and may not provide long term clinical benefits. To overcome this obstacle for effective treatment the applications of two or more drugs are preferable. A limitation of multidrug use is the varying pharmacokinetics of different drugs. To overcome these impediments, we designed and synthesized multi-layered polyvinyl alcohol tethered hollow manganese ferrite nanocarriers capable of encapsulating two drugs with unique attributes of sensitivity towards tumor acidic milieu, mono-dispersive, compactness and high encapsulation efficiency. We encapsulated tamoxifen and diosgenin in the peripheral and subsequent inner layers of multilayered nanocarriers. In vitro and in vivo studies evaluated the nanocarrier uptake and retention ability of the tumor through magnetic saturation studies and elucidated the molecular mechanisms mediating drug(s)-induced apoptosis. The acidity of the tumor environment triggers extracellular dissociation of the peripheral coats resulting in release of tamoxifen blocking the estrogen receptor. The partially degraded nanocarriers localize intracellularly through endosomal escape and release diosgenin. Nanocarrier treatment reduced the cellular levels of Bcl2 and p53, while increasing the levels of Bim. This delivery system successfully embodies the sequential release of drugs and may provide a therapeutic strategy for sequentially affecting multiple targets in advanced cancers.

11.
J Phys Chem B ; 118(40): 11667-76, 2014 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-25247718

RESUMO

Pathogenesis of amyloid-related diseases is related to nonnative folding of proteins with the formation of insoluble deposits in the extracellular space of various tissues. Having the unique properties of small size, large surface area, biodegradability, and relative nontoxicity, magnetic nanoparticles have drawn a lot of attention in biomedical applications. Herein, we demonstrate the effect of bare and differently functionalized magnetic MnFe2O4 nanoparticles on fibrillation of human serum albumin in vitro. The process has been monitored using Thioflavin T fluorescence, Congo red binding assay, circular dichroism, fluorescence microscopy, and transmission electron microscopy. From our experimental results, amine functionalized MnFe2O4 nanoparticles are found to inhibit formation of fibrils more effectively than bare ones, while carboxylated nanoparticles do not have a significant effect on fibrillation. This study has explored the prospects of using specific magnetic nanoparticles with appropriate modification to control self-assembly of proteins and may act as a precursor in therapeutic applications.


Assuntos
Amiloide/antagonistas & inibidores , Amiloide/química , Compostos Férricos/química , Compostos Férricos/farmacologia , Nanopartículas de Magnetita/química , Compostos de Manganês/química , Compostos de Manganês/farmacologia , Albumina Sérica/química , Albumina Sérica/ultraestrutura , Aminação , Amiloide/ultraestrutura , Humanos , Modelos Moleculares , Conformação Proteica/efeitos dos fármacos
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