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Current conventional mono and combination therapeutic strategies often fail to target breast cancer tissue effectively due to tumor heterogeneity comprising cancer stem cells (CSCs) and bulk tumor cells. This is further associated with drug toxicity and resistivity in the long run. A nanomedicine platform incorporating combination anti-cancer treatment might overcome these challenges and generate synergistic anti-cancer effects and also reduce drug toxicity. GANT61 and curcumin were co-delivered via polymeric nanoparticles (NPs) for the first time to elicit enhanced anti-tumor activity against heterogeneous breast cancer cell line MCF-7. We adopted the single-emulsion-solvent evaporation method for the preparation of the therapeutic NPs. The GANT61-curcumin PLGA NPs were characterized for their size, shape and chemical properties, and anti-cancer cell studies were undertaken for the plausible explanation of our hypothesis. The synthesized GANT61-curcumin PLGA NPs had a spherical, smooth surface morphology, and an average size of 347.4 d. nm. The NPs induced cytotoxic effects in breast cancer cells at a mid-minimal dosage followed by cell death via autophagy and apoptosis, reduction in their target protein expression along with compromising the self-renewal property of CSCs as revealed by their in vitro cell studies. The dual-drug NPs thus provide a novel perspective on aiding existing anti-cancer nanomedicine therapies to target a heterogeneous tumor mass effectively.
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Neoplasias da Mama/tratamento farmacológico , Curcumina/uso terapêutico , Nanopartículas/química , Fosfatidilinositol 3-Quinases/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piridinas/uso terapêutico , Pirimidinas/uso terapêutico , Proteína GLI1 em Dedos de Zinco/metabolismo , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/ultraestrutura , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Neoplasias da Mama/patologia , Neoplasias da Mama/ultraestrutura , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcumina/farmacologia , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Feminino , Humanos , Células MCF-7 , Camundongos , Nanopartículas/ultraestrutura , Tamanho da Partícula , Espectroscopia Fotoeletrônica , Piridinas/farmacologia , Pirimidinas/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/patologia , Eletricidade EstáticaRESUMO
Details of a fast and sustainable bottom-up process to grow large area high quality graphene films without the aid of any catalyst are reported in this paper. We used Melaleuca alternifolia, a volatile natural extract from tea tree plant as the precursor. The as-fabricated graphene films yielded a stable contact angle of 135°, indicating their potential application in very high hydrophobic coatings. The electronic devices formed by sandwiching pentacene between graphene and aluminum films demonstrated memristive behavior, and hence, these graphene films could find use in nonvolatile memory devices also.
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BACKGROUND: Gliomas have been termed recurrent cancers due to their highly aggressive nature. Their tendency to infiltrate and metastasize has posed significant roadblocks to in attaining fool proof treatment solutions. An initiative to curb such a scenario was successfully demonstrated in vitro, utilizing a multi-conceptual gold nanoparticle based photo-thermal and drug combination therapy. METHODS: Gold nanoparticles (Au NPs) were synthesized with a highly environmentally benign process. The Au NPs were PEGylated and conjugated with folate and transferrin antibody to achieve a dual targeted nano-formulation directed towards gliomas. Curcin, a type 1 ribosome inactivating protein, was attached to the Au NPs as the drug candidate, and its multifarious toxic aspects analyzed in vitro. NIR photo-thermal properties of the Au nano-conjugates were studied to selectively ablate the glioma cancer colonies. RESULTS: Highly cyto-compatible, 10-15nm Au NP conjugates were synthesized with pronounced specificity towards gliomas. Curcin was successfully conjugated to the Au NPs with pH responsive drug release. Prominent toxic aspects of curcin, such as ROS generation, mitochondrial and cytoskeletal destabilization were witnessed. Excellent photo-thermal ablation properties of gold nanoparticles were utilized to completely disrupt the cancer colonies with significant precision. CONCLUSION: The multifunctional nanoconjugate projects its competence in imparting complete arrest of the future proliferation or migration of the cancer mass. GENERAL SIGNIFICANCE: With multifunctionality the essence of nanomedicine in recent years, the present nanoconjugate highlights itself as a viable option for a multimodal treatment option for brain cancers and the like.
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Neoplasias Encefálicas/tratamento farmacológico , Ouro/administração & dosagem , Nanopartículas Metálicas/administração & dosagem , Proteínas Inativadoras de Ribossomos Tipo 1/administração & dosagem , Células Cultivadas , Humanos , Espécies Reativas de Oxigênio/metabolismo , TricotecenosRESUMO
Nonspecificity and cardiotoxicity are the primary limitations of current doxorubicin chemotherapy. To minimize side effects and to enhance bioavailability of doxorubicin to cancer cells, a dual-targeted pH-sensitive biocompatible polymeric nanosystem was designed and developed. An ATRP-based biodegradable triblock copolymer, poly(poly(ethylene glycol) methacrylate)-poly(caprolactone)-poly(poly(ethylene glycol) methacrylate) (pPEGMA-PCL-pPEGMA), conjugated with doxorubicin via an acid-labile hydrazone bond was synthesized and characterized. Dual targeting was achieved by attaching folic acid and the AS1411 aptamer through EDC-NHS coupling. Nanoparticles of the functionalized triblock copolymer were prepared using the nanoprecipitation method, resulting in an average particle size of â¼140 nm. The biocompatibility of the nanoparticles was evaluated using MTT cytotoxicity assays, blood compatibility studies, and protein adsorption studies. In vitro drug release studies showed a higher cumulative doxorubicin release at pH 5.0 (â¼70%) compared to pH 7.4 (â¼25%) owing to the presence of the acid-sensitive hydrazone linkage. Dual targeting with folate and the AS1411 aptamer increased the cancer-targeting efficiency of the nanoparticles, resulting in enhanced cellular uptake (10- and 100-fold increase in uptake compared to single-targeted NPs and non-targeted NPs, respectively) and a higher payload of doxorubicin in epithelial cancer cell lines (MCF-7 and PANC-1), with subsequent higher apoptosis, whereas a normal (noncancerous) cell line (L929) was spared from the adverse effects of doxorubicin. The results indicate that the dual-targeted pH-sensitive biocompatible polymeric nanosystem can act as a potential drug delivery vehicle against various epithelial cancers such as those of the breast, ovary, pancreas, lung, and others.
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Antineoplásicos/farmacologia , Materiais Biocompatíveis/farmacologia , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Ácido Fólico/farmacologia , Nanopartículas/química , Oligodesoxirribonucleotídeos/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Aptâmeros de Nucleotídeos , Materiais Biocompatíveis/administração & dosagem , Materiais Biocompatíveis/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Ensaios de Seleção de Medicamentos Antitumorais , Ácido Fólico/administração & dosagem , Ácido Fólico/química , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Estrutura Molecular , Nanopartículas/administração & dosagem , Oligodesoxirribonucleotídeos/administração & dosagem , Oligodesoxirribonucleotídeos/química , Tamanho da Partícula , Polimerização , Relação Estrutura-Atividade , Propriedades de SuperfícieRESUMO
Sulfated polysaccharides are complex polysaccharide molecules with excellent physico-chemical properties and bioactivities. On the basis of origin, they are classified as plant, animal, microbial and chemically synthesized sulfated polysaccharides. They have been widely applied in the fields of material and biological sciences. Biocompatibility and biodegradability of these molecules facilitate their increased use in the nanoparticle synthesis and tissue engineering applications. This review focuses on the structure, function and applications of important types of natural and chemically derived sulfated polysaccharides in the fields of nanotechnology and biomedical sciences. In the first part, we discuss the classification and role of sulfated polysaccharides in various fields. Later, we elaborate the specific bionano applications of commercially important sulfated polysaccharides in ionic gelation, stabilizing, cross-linking, capping and encapsulation of drugs. Finally, we conclude with the future scope and advanced applications of sulfated polysaccharides in various fields of interdisciplinary science. FROM THE CLINICAL EDITOR: This comprehensive review focuses on the structure, function, and applications of natural and chemically derived sulfated polysaccharides in the fields of nanotechnology and biomedical sciences.
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Tecnologia Biomédica , Sistemas de Liberação de Medicamentos , Nanotecnologia , Polissacarídeos/química , Humanos , Polissacarídeos/classificação , Sulfatos/química , Engenharia TecidualRESUMO
The targeting and therapeutic efficacy of dye- and dual-drug-loaded silica nanoparticles, functionalized with triple targeting ligands specific towards cancer and neoangiogenesis simultaneously, are discussed. This synergized, high-precision, multitarget concept culminates in an elevated uptake of nanoparticles by cancer and angiogenic cells with amplified proficiency, thereby imparting superior therapeutic efficacy against breast cancer cells and completely disabling the migration and angiogenic sprouting ability of activated endothelial cells. The exceptional multimodal efficiency achieved by this single therapeutic nanoformulation holds promise for the synergistic targeting and treatment of the yet elusive cancer and its related angiogenesis in a single, lethal shot.
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Nanomedicina/métodos , Neoplasias/terapia , Neovascularização Patológica , Inibidores da Angiogênese/química , Animais , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Cetrimônio , Compostos de Cetrimônio/química , Sistemas de Liberação de Medicamentos , Sinergismo Farmacológico , Células Endoteliais/efeitos dos fármacos , Feminino , Corantes Fluorescentes/química , Células Endoteliais da Veia Umbilical Humana , Humanos , Ligantes , Lipídeos/química , Células MCF-7 , Camundongos , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Nanopartículas , Polietilenoglicóis/química , Dióxido de Silício/químicaRESUMO
Liposomes and polymers are widely used drug carriers for controlled release since they offer many advantages like increased treatment effectiveness, reduced toxicity and are of biodegradable nature. In this work, anticancer drug-loaded PLGA-lecithin-PEG nanoparticles (NPs) were synthesized and were functionalized with AS1411 anti-nucleolin aptamers for site-specific targeting against tumor cells which over expresses nucleolin receptors. The particles were characterized by transmission electron microscope (TEM) and X-ray photoelectron spectroscopy (XPS). The drug-loading efficiency, encapsulation efficiency and in vitro drug release studies were conducted using UV spectroscopy. Cytotoxicity studies were carried out in two different cancer cell lines, MCF-7 and GI-1 cells and two different normal cells, L929 cells and HMEC cells. Confocal microscopy and flowcytometry confirmed the cellular uptake of particles and targeted drug delivery. The morphology analysis of the NPs proved that the particles were smooth and spherical in shape with a size ranging from 60 to 110 nm. Drug-loading studies indicated that under the same drug loading, the aptamer-targeted NPs show enhanced cancer killing effect compared to the corresponding non-targeted NPs. In addition, the PLGA-lecithin-PEG NPs exhibited high encapsulation efficiency and superior sustained drug release than the drug loaded in plain PLGA NPs. The results confirmed that AS1411 aptamer-PLGA-lecithin-PEG NPs are potential carrier candidates for differential targeted drug delivery.
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Antineoplásicos/farmacocinética , Portadores de Fármacos/farmacocinética , Ácido Láctico/farmacocinética , Lecitinas/farmacocinética , Nanopartículas/química , Oligodesoxirribonucleotídeos/farmacocinética , Polietilenoglicóis/farmacocinética , Ácido Poliglicólico/farmacocinética , Aptâmeros de Nucleotídeos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Citometria de Fluxo , Humanos , Ácido Láctico/química , Lecitinas/química , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Oligodesoxirribonucleotídeos/química , Espectroscopia Fotoeletrônica , Polietilenoglicóis/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Espectrofotometria UltravioletaRESUMO
The use of fluorescent nanomaterials has gained great importance in the field of medical imaging. Many traditional imaging technologies have been reported utilizing dyes in the past. These methods face drawbacks due to non-specific accumulation and photobleaching of dyes. We studied the uptake and internalization of two different sized (30 nm and 100 nm) FITC labeled silica nanoparticles in Human umbilical vein endothelial cell line. These nanomaterials show high biocompatability and are highly photostable inside live cells for increased period of time in comparison to the dye alone. To our knowledge, we report for the first time the use of 30 nm fluorescent silica nanoparticles as efficient endothelial tags along with the well studied 100 nm particles. We also have emphasized the good photostability of these materials in live cells.
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Materiais Biocompatíveis/metabolismo , Células Endoteliais/metabolismo , Fluoresceína-5-Isotiocianato/metabolismo , Corantes Fluorescentes/metabolismo , Nanopartículas/química , Dióxido de Silício/química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Sobrevivência Celular , Células Cultivadas , Células Endoteliais/citologia , Fluoresceína-5-Isotiocianato/síntese química , Fluoresceína-5-Isotiocianato/química , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Humanos , Tamanho da Partícula , Processos Fotoquímicos , Propriedades de SuperfícieRESUMO
Cancer stands as a leading cause of mortality worldwide and diagnostics of cancer still faces drawbacks. Optical imaging of cancer would allow early diagnosis, evaluation of disease progression and therapy efficiency. To that aim, we have developed highly biocompatible PEG functionalized cadmium chalcogenide based three differently luminescent quantum dots (QDs) (CdS, CdSe and CdTe). Folate targeting scheme was utilized for targeting cancer cell line, MCF-7. We demonstrate the biocompatibility, specificity and efficiency of our nanotool in detection of cancer cells sparing normal cell lines with retained fluorescence of functionalized QDs as parental counterpart. This is the first time report of utilizing three differently fluorescent QDs and we have detailed about the internalization of these materials and time dependent saturation of targeting schemes. We present here the success of utilizing our biocompatible imaging tool for early diagnosis of cancer.
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Cádmio/química , Calcogênios/química , Materiais Revestidos Biocompatíveis/análise , Substâncias Luminescentes/análise , Imagem Molecular/métodos , Neoplasias/diagnóstico , Polietilenoglicóis/química , Pontos Quânticos , Proliferação de Células , Materiais Revestidos Biocompatíveis/síntese química , Materiais Revestidos Biocompatíveis/química , Humanos , Substâncias Luminescentes/síntese química , Substâncias Luminescentes/química , Neoplasias/patologia , Tamanho da Partícula , Propriedades de Superfície , Células Tumorais CultivadasRESUMO
For the successful diverse applications of different nanomaterials in life sciences, it is necessary to understand the ultimate fate, distribution and potential environmental impacts of manufactured nanomaterials. Phytotoxicity studies using higher plants is an important criterion for understanding the toxicity of engineered nanomaterials. We studied the effects of engineered carbon nanomaterials of various dimensionalities (carbon nanotubes, C60, graphene) on the germination of rice seeds. A pronounced increase in the rate of germination was observed for rice seeds in the presence of some of these carbon nanostructures, in particular the nanotubes. Increased water content was observed in the carbon nanomaterial treated seeds during germination compared to controls. The germinated seeds were then grown in a basal growth medium supplemented with carbon nanomaterials for studying their impact on further seedling growth. Treated seedlings appeared to be healthier with well-developed root and shoot systems compared to control seedlings. Our results indicate the possible use for carbon nanomaterials as enhancers in the growth of rice seedlings.
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Carbono/farmacologia , Germinação/efeitos dos fármacos , Nanoestruturas , Oryza/fisiologia , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Oryza/embriologia , Oryza/crescimento & desenvolvimento , Sementes/fisiologia , TermogravimetriaRESUMO
The use of fluorescent nanomaterials with good photostability and biocompatibility in live imaging of cells has gained increased attention. Even though several imaging techniques have been reported for mammalian cells, very limited literatures are available for nanomaterial based live imaging in plant system. We studied the uptake ability of two different nanomaterials, the highly photostable CdSe quantum dots and highly biocompatible FITC-labeled silica nanoparticles by rice seedlings which could provide greater opportunities for developing novel in vivo imaging techniques in plants. The effects of these nanomaterials on rice seed germination have also been studied for analyzing their phytotoxic effects on plants. We observed good germination of seeds in the presence of FITC-labeled silica nanoparticles whereas germination was arrested with quantum dots. The uptake of both the nanomaterials has been observed with rice seedlings, which calls for more research for recommending their safe use as biolabels in plants.
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Fluoresceína-5-Isotiocianato/química , Corantes Fluorescentes/química , Nanopartículas/química , Oryza/química , Pontos Quânticos , Plântula/química , Dióxido de Silício/química , GerminaçãoRESUMO
Self-assembled magnetic colloidal suspensions are sought after by material scientists owing to its huge application potential. The biomedical applications of colloidal nanoparticles necessitate that they are biocompatible, non-interacting, monodispersed and hence the synthesis of such nanostructures has great relevance in the realm of nanoscience. Silica-coated superparamagnetic iron oxide nanoparticles based ferrofluids were prepared using polyethylene glycol as carrier fluid by employing a controlled co-precipitation technique followed by a modified sol-gel synthesis. A plausible mechanism for the formation of stable suspension of SiO2-coated Iron Oxide nanoparticles with a size of about 9 nm dispersed in polyethylene glycol (PEG) is proposed. Core-shell nature of the resultant SiO2-Iron Oxide nanocomposite was verified using transmission electron microscopy. Fourier transform-infrared spectroscopy studies were carried out to understand the structure and nature of chemical bonds. The result suggests that Iron Oxide exist in an isolated state inside silica matrix. Moreover, the presence of silanol bonds establishes the hydrophilic nature of silica shell confirming the formation of stable ferrofluid with PEG as carrier fluid. The magnetic characterization reveals the superparamagnetic behavior of the nanoparticles with a rather narrow distribution of blocking temperatures. These properties are not seen in ferrofluids prepared from Iron Oxide nanoparticles without SiO2 coating. The latter suggests the successful tuning of the inter-particle interactions preventing agglomeration of nanoparticles. Cytotoxicity studies on citric acid coated water based ferrofluid and silica-coated PEG-based ferrofluid were evaluated by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium chloride assay and it shows an enhanced compatibility for silica modified nanoparticles.
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Materiais Biocompatíveis/síntese química , Sobrevivência Celular/efeitos dos fármacos , Compostos Férricos/química , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Dióxido de Silício/química , Materiais Biocompatíveis/farmacologia , Cristalização/métodos , Células HeLa , Humanos , Magnetismo , Teste de Materiais , Tamanho da Partícula , SoluçõesRESUMO
The emergence of pH-sensitive nanoscale particles is beneficial due to their ability to only release cargo in a colonic pH environment, which helps to directly target inflamed tissues in inflammatory bowel disease (IBD). Hence, we have designed the formulation of pH-sensitive biodegradable garcinol (GAR)-loaded poly (lactic-co-glycolic acid) (PLGA) coated with Eudragit® S100 (ES100) (GAR-PLGA-ES100 nanoparticles (NPs)) for reducing inflammation caused by proinflammatory cytokines. The GAR-PLGA-ES100 NPs were prepared using a solvent evaporation technique and characterized for shape and surface morphology. An in vitro drug release study revealed the release of the drug specifically from NPs at the colonic pH of 7.4. The in vitro cytotoxicity of the GAR-PLGA-ES100 NPs was also evaluated and found to be highly biocompatible with CACO-2 cells. These NPs were able to reduce lactate dehydrogenase (LDH) and myeloperoxidase (MPO) activity. Inhibition of the expression of pro-inflammatory cytokine TNF-α , chemokine interleukin (IL)-8 and the nuclear factor kappa light chain enhancer of activated B-cells (NF-κB) was observed after GAR-PLGA-ES100 NPs treatment. Therefore, our results support the idea that GAR-PLGA-ES100 NPs show substantial improvement after the release of the drug, specifically in colonic pH targeting and reduction in the activation of inflammation that leads to IBD, suggesting that GAR-PLGA-ES100 NPs are promising candidates for oral delivery to colonic inflamed tissue.
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Atherosclerosis is Caesar's sword, which poses a huge risk to the present generation. Understanding the atherosclerotic disease cycle would allow ensuring improved diagnosis, better care, and treatment. Unfortunately, a highly effective and safe way of treating atherosclerosis in the medical community remains a continuous challenge. Conventional treatments have shown considerable success, but have some adverse effects on the human body. Natural derived medications or nutraceuticals have gained immense popularity in the treatment of atherosclerosis due to their decreased side effects and toxicity-related issues. In hindsight, the contribution of nutraceuticals in imparting enhanced clinical efficacy against atherosclerosis warrants more experimental evidence. On the other hand, nanotechnology and drug delivery systems (DDS) have revolutionized the way therapeutics are performed and researchers have been constantly exploring the positive effects that DDS brings to the field of therapeutic techniques. It could be as exciting as ever to apply nano-mediated delivery of nutraceuticals as an additional strategy to target the atherosclerotic sites boasting high therapeutic efficiency of the nutraceuticals and fewer side effects.
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Aterosclerose/tratamento farmacológico , Suplementos Nutricionais , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Aterosclerose/fisiopatologia , Química Farmacêutica , Endotélio Vascular/fisiopatologia , Células Espumosas/metabolismo , Fatores de Risco de Doenças Cardíacas , Humanos , Mediadores da Inflamação/metabolismo , Lipídeos/química , Nanopartículas Metálicas/química , Placa Aterosclerótica/fisiopatologia , Polímeros/químicaRESUMO
Cholesterol-rich arterial plaques characterize atherosclerosis, a significant cause of heart disease. Nutraceuticals have received attention over the years, demonstrating potential benefits towards treating and preventing cardiovascular diseases (CVD), including atherosclerosis. Curcumin, a potent polyphenol present in Curcuma longa, has shown remarkable anti-atherosclerotic activity via anti-inflammatory and anti-oxidative properties. The bioavailability and low water solubility of curcumin limit its clinical translational purposes. These issues can be circumvented effectively by nano-drug delivery systems that can target atherosclerotic plaque sites. In this work, we chose to use curcumin and a natural bioenhancer called Bioperine (derived from Piper nigrum) inside a polymeric nano-drug delivery system for targeting atherosclerotic plaque sites. We selected two different ratios of curcumin:Bioperine to study its comparative effect on the inhibition of oxidized low-density lipoprotein (Ox-LDL)-induced foam cell formation. Our studies demonstrated that Cur-Bio PLGA NPs (both ratios) maintained the cell viability in THP-1 monocyte-derived macrophages above 80% at all periods. The 1:0.2:10 ratio of Cur-Bio PLGA NPs at a concentration of 250 µg/mL illustrated an enhanced reduction in the relative cholesterol content in the THP-1-derived foam cells compared to the 1:1:10 ratio. Confocal microscopy analysis also revealed a reduction in macrophage-mediated foam cell formation when administered with both the ratios of Cur-Bio PLGA NPs. Relative fold change in the mRNA expression of the genes involved in the inflammatory pathways in the atherosclerotic process downregulated NF-κB, CCL2/MCP-1, CD-36, and STAT-3 activity while upregulating the SCAR-B1 expression when treated with the Cur-Bio PLGA NPs. This study thus highlights the importance of natural-based compounds towards the therapeutic intervention against atherosclerotic activity when administered as preventive medicine.
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Magnetic analogue of an isolated free electric charge, i.e., a magnet with a single north or south pole, is a long sought-after particle which remains elusive so far. In magnetically frustrated pyrochlore solids, a classical analogue of monopole was observed as a result of excitation of spin ice vertices. Direct visualization of such excitations were proposed and later confirmed in analogous artificial spin ice (ASI) systems of square as well as Kagome geometries. However, such magnetically charged vertices are randomly created as they are thermally driven and are always associated with corresponding equal and opposite emergent charges, often termed as monopole-antimonopole pairs, connected by observable strings. Here, we demonstrate a controlled stabilisation of a robust isolated emergent monopole-like magnetically charged vertices in individual square ASI systems by application of an external magnetic field. The excitation conserves the magnetic charge without the involvement of a corresponding excitation of opposite charge. Well supported by Monte Carlo simulations our experimental results enable, in absence of a true elemental magnetic monopole, creation of electron vortices and studying electrodynamics in presence of a monopole-like field in a solid state environment.
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Developments in nanotechnology have paved the way for the early detection, treatment, and prevention of several tumors which affect mankind. In the past few years, near-infrared (NIR) fluorescence imaging techniques have emerged that enable the in vivo imaging of physiological, metabolic, and molecular function. The NIR window, also known as the diagnostic window (700-900 nm), can be explored for sensitive detection techniques. Nanoparticles, particularly semiconductor quantum dots (QDs), can be utilized for the purpose of optical imaging. These semiconductor QDs possess novel electronic, optical, magnetic, and structural properties which are quite different from those of bulk materials. NIR QDs with these unique properties can be utilized as contrast agents for optical imaging, particularly for deep tissue imaging. Deep tissue imaging provides more information about the pathological status of the disease, which makes the treatment more effective and efficient. In this review we highlight the importance of NIR QDs as probes for optical imaging. We describe the different types of NIR QDs, their synthesis, and their application for deep tissue imaging along with recently developed self-illuminating NIR QDs.
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Diagnóstico por Imagem/métodos , Imagem Molecular/métodos , Pontos Quânticos , Animais , Corantes Fluorescentes/química , Humanos , Espectroscopia de Luz Próxima ao Infravermelho , Distribuição TecidualRESUMO
The human intestine, which harbors trillions of symbiotic microorganisms, may enter into dysbiosis when exposed to a genetic defect or environmental stress. The naissance of chronic inflammation due to the battle of the immune system with the trespassing gut bacteria leads to the rise of inflammatory bowel disease (IBD). Though the genes behind the scenes and their link to the disease are still unclear, the onset of IBD occurs in young adults and has expanded from the Western world into the newly industrialized countries. Conventional drug deliveries depend on a daily heavy dosage of immune suppressants or anti-inflammatory drugs targeted for the treatment of two types of IBD, ulcerative colitis (UC) and Crohn's disease (CD), which are often associated with systemic side effects and adverse toxicities. Advances in oral delivery through nanotechnology seek remedies to overcome the drawbacks of these conventional drug delivery systems through improved drug encapsulation and targeted delivery. In this review, we discuss the association of genetic factors, the immune system, the gut microbiome, and environmental factors like diet in the pathogenesis of IBD. We also review the various physiological concerns required for oral delivery to the gastrointestinal tract (GIT) and new strategies in nanotechnology-derived, colon-targeting drug delivery systems.
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The evolving dynamics of drug resistance due to tumor heterogeneity often creates impediments to traditional therapies making it a challenging issue for cancer cure. Breast cancer often faces challenges of current therapeutic interventions owing to its multiple complexities and high drug resistivityï¼ for example against drugs like trastuzumab and tamoxifen. Drug resistance in the majority of breast cancer is often aided by the overtly expressed P-glycoprotein (P-gp) that guides in the rapid drug efflux of chemotherapy drugs. Despite continuous endeavors and ground-breaking achievements in the pursuit of finding better cancer therapeutic avenues, drug resistance is still a menace to hold back. Among newer therapeutic approaches, the application of phytonutrients such as alkaloids to suppress P-gp activity in drug-resistant cancers has found an exciting niche in the arena of alternative cancer therapies. In this work, we would like to present a black pepper alkaloid derivative known as BioPerine-loaded chitosan (CS)-polyethylene glycol (PEG) coated polylactic acid (PLA) hybrid polymeric nanoparticle to improve the bioavailability of BioPerine and its therapeutic efficacy in suppressing P-gp expression in MDA-MB 453 breast cancer cell line. Our findings revealed that the CS-PEG-BioPerine-PLA nanoparticles demonstrated a smooth spherical morphology with an average size of 316 nm, with improved aqueous solubility, and provided sustained BioPerine release. The nanoparticles also enhanced in vitro cytotoxicity and downregulation of P-gp expression in MDA-MB 453 cells compared to the commercial inhibitor verapamil hydrochloride, thus promising a piece of exciting evidence for the development of BioPerine based nano-drug delivery system in combination with traditional therapies as a crucial approach to tackling multi-drug resistance in cancers.
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Drugs targeting heat shock protein 90 (Hsp90) have been extensively explored for their anticancer potential in advanced clinical trials. Nanoformulations have been an important drug delivery platform for the anticancer molecules like Hsp90 inhibitors. It has been reported that bovine serum albumin (BSA) nanoparticles (NPs) serve as carriers for anticancer drugs, which have been extensively explored for their therapeutic efficacy against cancers. Luminespib (also known as NVP-AUY922) is a new generation Hsp90 inhibitor that was introduced recently. It is one of the most studied Hsp90 inhibitors for a variety of cancers in Phase I and II clinical trials and is similar to its predecessors such as the ansamycin class of molecules. To our knowledge, nanoformulations for luminespib remain unexplored for their anticancer potential. In the present study, we developed aqueous dispensable BSA NPs for controlled delivery of luminespib. The luminespib-loaded BSA NPs were characterized by SEM, TEM, FTIR, XPS, UV-visible spectroscopy and fluorescence spectroscopy. The results suggest that luminespib interacts by non-covalent reversible interactions with BSA to form drug-loaded BSA NPs (DNPs). Our in vitro evaluations suggest that DNP-based aqueous nanoformulations can be used in both pancreatic (MIA PaCa-2) and breast (MCF-7) cancer therapy.