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1.
J Control Release ; 366: 282-296, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38123071

RESUMO

Poly-ethylene-glycol (PEG)-based nanoparticles (NPs) - including cylindrical micelles (CNPs), spherical micelles (SNPs), and PEGylated liposomes (PLs) - are hypothesized to be cleared in vivo by opsonization followed by liver macrophage phagocytosis. This hypothesis has been used to explain the rapid and significant localization of NPs to the liver after administration into the mammalian vasculature. Here, we show that the opsonization-phagocytosis nexus is not the major factor driving PEG-NP - macrophage interactions. First, mouse and human blood proteins had insignificant affinity for PEG-NPs. Second, PEG-NPs bound macrophages in the absence of serum proteins. Third, lipoproteins blocked PEG-NP binding to macrophages. Because of these findings, we tested the postulate that PEG-NPs bind (apo)lipoprotein receptors. Indeed, PEG-NPs triggered an in vitro macrophage transcription program that was similar to that triggered by lipoproteins and different from that triggered by lipopolysaccharide (LPS) and group A Streptococcus. Unlike LPS and pathogens, PLs did not increase transcripts involved in phagocytosis or inflammation. High-density lipoprotein (HDL) and SNPs triggered remarkably similar mouse bone-marrow-derived macrophage transcription programs. Unlike opsonized pathogens, CNPs, SNPs, and PLs lowered macrophage autophagosome levels and either reduced or did not increase the secretion of key macrophage pro-inflammatory cytokines and chemokines. Thus, the sequential opsonization and phagocytosis process is likely a minor aspect of PEG-NP - macrophage interactions. Instead, PEG-NP interactions with (apo)lipoprotein and scavenger receptors appear to be a strong driving force for PEG-NP - macrophage binding, entry, and downstream effects. We hypothesize that the high presence of these receptors on liver macrophages and on liver sinusoidal endothelial cells is the reason PEG-NPs localize rapidly and strongly to the liver.


Assuntos
Células Endoteliais , Lipopolissacarídeos , Humanos , Animais , Camundongos , Micelas , Macrófagos , Fatores Imunológicos , Fagocitose , Lipoproteínas , Mamíferos
2.
RSC Adv ; 12(27): 17321-17329, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35765434

RESUMO

In this study hybrid nanocomposites (HNCs) based on manganese oxides (MnO x /Mn3O4) and reduced graphene oxide (rGO) are synthesized as active electrodes for energy storage devices. Comprehensive structural characterizations demonstrate that the active material is composed of MnO x /Mn3O4 nanorods and nanoparticles embedded in rGO nanosheets. The development of such novel structures is facilitated by the extreme synthesis conditions (high temperatures and pressures) of the liquid-confined plasma plume present in the Laser Ablation Synthesis in Solution (LASiS) technique. Specifically, functional characterizations demonstrate that the performance of the active layer is highly correlated with the MnO x /Mn3O4 to rGO ratio and the morphology of MnO x /Mn3O4 nanostructures in HNCs. To that end, active layer inks comprising HNC samples prepared under optimal laser ablation time windows, when interfaced with a percolated conductive network of electronic grade graphene and carbon nanofibers (CNFs) mixture, indicate superior supercapacitance for functional electrodes fabricated via sequential inkjet printing of the substrate, current collector layer, active material layer, and gel polymer electrolyte layer. Electrochemical characterizations unequivocally reveal that the electrode with the LASiS synthesized MnO x /Mn3O4-rGO composite exhibits significantly higher specific capacitance compared to the ones produced with commercially available Mn3O4-graphene NCs. Moreover, the galvanostatic charge-discharge (GCD) experiments with the LASiS synthesized HNCs show a significantly larger charge storage capacity (325 F g-1) in comparison to NCs synthesized with commercially available Mn3O4-graphene (189 F g-1). Overall, this study has paved the way for use of LASiS-based synthesized functional material in combination with additive manufacturing techniques for all-printed electronics with superior performance.

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