RESUMO
In this contribution, we report the fabrication of multifunctional nanoparticles with gold shell over an iron oxide nanoparticles (INPs) core. The fabricated system combines the magnetic property of INPs and the surface plasmon resonance of gold. The developed nanoparticles are coated with thiolated pectin (TPGINs), which provides stability to the nanoparticles dispersion and allows the loading of hydrophobic anticancer drugs. Curcumin (Cur) is used as the model drug and an encapsulation efficiency of approximately 80% in TPGINs is observed. Cytotoxicity study with HeLa cells shows that Cur-loaded TPGINs have better viability percent (~30%) than Cur alone (~40%) at a dose of 30 µg of TPGINs. Further, annexin V-PI assay demonstrated the enhanced anticancer activity of Cur-loaded TPGINs via induction of apoptosis. The use of TPGINs leads to a significant enhancement in generating reactive oxygen species (ROS) in HeLa cells through improved radiosensitization by gamma irradiation (0.5 Gy). TPGINs are further evaluated for imparting contrast in magnetic resonance imaging (MRI) with the r2 relaxivity in the range of 11.06-13.94 s-1 µg-1 mL when measured at 7 Tesla. These experimental results indicate the potential of TPGINs for drug delivery and MR imaging.
Assuntos
Diagnóstico por Imagem , Nanopartículas Multifuncionais/química , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Pectinas/química , Tolerância a Radiação , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcumina/farmacologia , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Células HeLa , Humanos , Hidrodinâmica , Cinética , Imageamento por Ressonância Magnética , Nanopartículas Multifuncionais/ultraestrutura , Tamanho da Partícula , Imagens de Fantasmas , Espectroscopia Fotoeletrônica , Espécies Reativas de Oxigênio/metabolismo , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , Coloração e Rotulagem , TermogravimetriaRESUMO
Respiratory Syncytial Virus (RSV) has been a major health concern globally for decades, yet no effective prophylactic or treatment regimen is available. The key viral proteins responsible for RSV pathology include the fusion protein (F), the immunomodulatory non-structural-protein 1 (NS1) and the phosphoprotein (P) involved in viral replication. Herein, we developed a novel shell-core multifunctional nanosystem with dual payload: a plasmid construct encoding for shRNAs against NS1 and P, and an anti-fusion peptide (HR2D). Anti-ICAM1 antibody conjugated on the nanoparticle (NP) surface is used to target RSV infected cells. Our data show the potential of this nanosystem as a prophylactic and/or a therapeutic regimen against RSV infection. Furthermore, therapy of RSV infected mice with this nanosystem, in addition to reducing viral load, modulated expression of Th2 and allergy-associated cytokines such as IL4, IL-13 and IL-17 indicating a direct role of this nanosystem in the mechanisms involved in the immunoregulation of disease pathogenesis.
Assuntos
Nanopartículas Multifuncionais/uso terapêutico , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vírus Sincicial Respiratório Humano/fisiologia , Animais , Citocinas/metabolismo , Liberação Controlada de Fármacos , Feminino , Mediadores da Inflamação/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Camundongos Endogâmicos BALB C , Nanopartículas Multifuncionais/ultraestrutura , Peptídeos/farmacologia , Plasmídeos/genética , RNA Interferente Pequeno/metabolismo , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/efeitos dos fármacos , Transfecção , Proteínas Virais de Fusão/metabolismoRESUMO
Mobile microrobots offer great promise for minimally invasive targeted medical theranostic applications at hard-to-access regions inside the human body. The circulatory system represents the ideal route for navigation; however, blood flow impairs propulsion of microrobots especially for the ones with overall sizes less than 10 micrometers. Moreover, cell- and tissue-specific targeting is required for efficient recognition of disease sites and long-term preservation of microrobots under dynamic flow conditions. Here, we report cell-sized multifunctional surface microrollers with ~3.0 and ~7.8-micrometer diameters, inspired by leukocytes in the circulatory system, for targeted drug delivery into specific cells and controlled navigation inside blood flow. The leukocyte-inspired spherical microrollers are composed of magnetically responsive Janus microparticles functionalized with targeting antibodies against cancer cells (anti-HER2) and light-cleavable cancer drug molecules (doxorubicin). Magnetic propulsion and steering of the microrollers resulted in translational motion speeds up to 600 micrometers per second, around 76 body lengths per second. Targeting cancer cells among a heterogeneous cell population was demonstrated by active propulsion and steering of the microrollers over the cell monolayers. The multifunctional microrollers were propelled against physiologically relevant blood flow (up to 2.5 dynes per square centimeter) on planar and endothelialized microchannels. Furthermore, the microrollers generated sufficient upstream propulsion to locomote on inclined three-dimensional surfaces in physiologically relevant blood flow. The multifunctional microroller platform described here presents a bioinspired approach toward in vivo controlled propulsion, navigation, and targeted active cargo delivery in the circulatory system.
Assuntos
Sistemas de Liberação de Medicamentos/instrumentação , Robótica/instrumentação , Antineoplásicos/administração & dosagem , Materiais Biomiméticos , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Desenho de Equipamento , Hemodinâmica/fisiologia , Humanos , Magnetismo , Microtecnologia/instrumentação , Movimento (Física) , Nanopartículas Multifuncionais/química , Nanopartículas Multifuncionais/ultraestrutura , Medicina de Precisão/instrumentação , Propriedades de SuperfícieRESUMO
Using flexible structures and components of metal-organic framework (MOF) materials, we designed and developed an artificial nanozyme with dual functions of a catalyst and luminescent sensor specifically for the determination and degradation of hormone 17ß-estradiol (E2) and its derivatives (E1, E3, and EE2), a class of disruptors with strong effect on the human endocrine system. This nanozyme composed of the luminescent Tb3+ ion, catalytic coenzyme factor hemin, and light-harvesting ligand can be used to both degrade E2 like natural horseradish peroxidase (HRP) and sense E2 as low as 50 pM by its luminescence. The nanozyme catalyzes the decomposition of E2 and its derivatives through a mechanism of active hydroxyl radicals and oxidative high-valent iron-oxo intermediates. The prepared nanozyme is pluripotent, stable, and cheap and can replace the widely used combination of natural enzyme and chromogenic substrate. The present strategy of constructing artificial enzymes directly from functional units provides a new way for the design and development of smart, multifunctional artificial enzymes.
Assuntos
Disruptores Endócrinos/metabolismo , Estradiol/química , Hemina/química , Estruturas Metalorgânicas/química , Nanopartículas Multifuncionais/química , Peroxidase/química , Térbio/química , Materiais Biomiméticos/química , Catálise , Estradiol/análogos & derivados , Peróxido de Hidrogênio/química , Cinética , Ligantes , Luminescência , Microscopia Eletrônica de Varredura , Nanopartículas Multifuncionais/ultraestruturaRESUMO
As a member of flavonoids, the application of quercetin has been mainly focused on antioxidation study. Fabrication of multifunctional nanoplatforms with quercetin is limited. In the present study, water-soluble quercetin derived nanoparticles (QFNPs) were fabricated through the one pot synthesis strategy with Fe3+, quercetin and poly (vinyl pyrrolidone) (PVP). The raw materials were dissolved in absolute ethanol and the mixed together. After stirring at room temperature for 6â¯h, the QFNPs could be simply harvested by centrifugation without the need of time-consuming dialysis procedure. Due to the protective effect of PVP, the synthesized nanoparticles could be well dispersed in water with the hydrodynamic size about 23â¯nm. DPPH free radical scavenging capacity assay showed QFNPs could act as efficient antioxidant. Besides antioxidation activity, the QFNPs also exhibited good photothermal capacity. Temperature stability result suggested the good stability of QFNPs between 35 and 95⯰C. MTT and hemolysis assay showed the good biocompatibility of QFNPs. What's more, the QFNPs showed good cellular antioxidation activity and efficient photothermal killing effect to cancer cells (4T1 cells). The QFNPs could be promising nanoplatform for biomedical application.