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1.
Int J Mol Sci ; 22(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34360803

RESUMO

The aim of cancer immunotherapy is to reactivate autoimmune responses to combat cancer cells. To stimulate the immune system, immunomodulators, such as adjuvants, cytokines, vaccines, and checkpoint inhibitors, are extensively designed and studied. Immunomodulators have several drawbacks, such as drug instability, limited half-life, rapid drug clearance, and uncontrolled immune responses when used directly in cancer immunotherapy. Several strategies have been used to overcome these limitations. A simple and effective approach is the loading of immunomodulators onto gold-based nanoparticles (GNPs). As gold is highly biocompatible, GNPs can be administered intravenously, which aids in increasing cancer cell permeability and retention time. Various gold nanoplatforms, including nanospheres, nanoshells, nanorods, nanocages, and nanostars have been effectively used in cancer immunotherapy. Gold nanostars (GNS) are one of the most promising GNP platforms because of their unusual star-shaped geometry, which significantly increases light absorption and provides high photon-to-heat conversion efficiency due to the plasmonic effect. As a result, GNPs are a useful vehicle for delivering antigens and adjuvants that support the immune system in killing tumor cells by facilitating or activating cytotoxic T lymphocytes. This review represents recent progress in encapsulating immunomodulators into GNPs for utility in a cancer immunotherapeutic regimen.


Assuntos
Ouro/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imunoterapia , Nanopartículas Metálicas/uso terapêutico , Neoplasias , Humanos , Neoplasias/imunologia , Neoplasias/terapia , Linfócitos T Citotóxicos/imunologia
2.
Prep Biochem Biotechnol ; 50(9): 865-873, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32393146

RESUMO

Biosynthesis of silver nanoparticles (AgNPs) using plant extracts has become a promising alternative to the conventional chemical synthesis approach. In this study, cost-effective synthesis of AgNPs was attempted using leaves extract of Litchi chinensis. Bio-reduction reaction for the synthesis of NPs was checked by confirming the presence of AgNPs in solution by UV-vis spectrophotometry and with further characterization by fourier-transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM). Surface plasmon resonance (SPR) band showed absorption peak at 422 nm indicating the formation of AgNPs, and FTIR spectra confirmed the presence of biological molecules involved in AgNPs synthesis. TEM analysis revealed the spherical shape of AgNPs with particle size distribution in a range of 5-15 nm. Further, the biosynthesized AgNPs showed significant bactericidal and sporicidal activity against model spore former Bacillus subtilis. AgNPs at concentrations ranging from 25 to 100 µg/mL showed bactericidal activity with inhibition zone ranging from 4-19 mm and sporicidal activity at 100-200 µg/mL in a range of 4.46-61.6% with an exposure time of 2-8 h. These findings exhibit distinctive potential of biogenic AgNPs for their efficient use in developing novel bactericidal and sporicidal agent against spore forming bacilli.


Assuntos
Antibacterianos/química , Química Verde/métodos , Litchi/química , Nanopartículas Metálicas/química , Prata/química , Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Nanopartículas Metálicas/ultraestrutura , Folhas de Planta/química , Prata/farmacologia , Esporos Bacterianos/efeitos dos fármacos
3.
Chem Biol Drug Des ; 97(3): 774-794, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33191630

RESUMO

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase located at the extracellular matrix cell adhesion site. This kinase mediates downstream signalling cascades on the cell-extracellular matrix of integrins, cytokine receptors, growth factor receptors and G-protein-coupled receptors. Several studies have suggested the importance of FAK in cancer cell adhesion, motility, proliferation and survival and is over-expressed in cancer cells. There is a growing body of evidence indicating involvement of FAK-mediated signalling and functions in development of tumour cells, making FAK an emerging viable therapeutic target. There is substantial research impetus on development of small molecule FAK inhibitors that impact and inhibit the downstream pathways of FAK, subsequently modulating cancer progression and survival. A variety of scaffolds including hybrid scaffolds have been designed and synthesized with some translating into clinical trials. In addition to the reduction of metastasis and angiogenesis, these inhibitors are effective in inducing tumour cell apoptosis. In this paper, we provide an overview of FAK and analysis of design, synthesis and structure-activity relationship of small molecule FAK inhibitors reported till date. We have discussed FAK inhibitors in clinical trials and highlighted future prospects in the development of FAK inhibitors to augment the armamentarium of cancer therapeutics.


Assuntos
Proteína-Tirosina Quinases de Adesão Focal/antagonistas & inibidores , Inibidores de Proteínas Quinases/química , Adesão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Inibidores de Proteínas Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Tiadiazóis/química , Tiadiazóis/metabolismo , Tiadiazóis/farmacologia , Tiadiazóis/uso terapêutico
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