One-Step Synthesis of Small-Sized and Water-Soluble NaREF(4) Upconversion Nanoparticles for in Vitro Cell Imaging and Drug Delivery.
One-Step Synthesis of Small-Sized and Water-Soluble NaREF(4) Upconversion Nanoparticles for In Vitro Cell Imaging and Drug Delivery.
Filed under: Drug and Alcohol Rehabilitation
Chemistry. 2013 Jan 7;
Yang D, Dai Y, Ma P, Kang X, Cheng Z, Li C, Lin J
Small (2-28?nm) NaREF(4) (rare earth (RE)=Nd-Lu, Y) nanoparticles (NPs) were prepared by an oil/water two-phase approach. Meanwhile, hydrophilic NPs can be obtained through a successful phase-transition process by introducing the amphiphilic surfactant sodium dodecylsulfate (SDS) into the same reaction system. Hollow-structured NaREF(4) (RE=Y, Yb, Lu) NPs can be fabricated in situ by electron-beam lithography on solid NPs. The MTT assay indicates that these hydrophilic NPs with hollow structures exhibit good biocompatibility. The as-prepared hollow-structured NPs can be used as anti-cancer drug carriers for drug storage/release investigations. Doxorubicin hydrochloride (DOX) was taken as model drug. The release of DOX from hollow ?-NaLuF(4) :20?%?Yb(3+) , 2?%?Er(3+) exhibits a pH-sensitive release patterns. Confocal microscopy observations indicate that the NPs can be taken up by HeLa cells and show obvious anti-cancer efficacy. Furthermore, ?-NaLuF(4) :20?%?Yb(3+) , 2?%?Er(3+) NPs show bright-red emission under IR excitation, making both the excitation and emission light fall within the “optical window” of biological tissues. The application of ?-NaLuF(4) :20?%?Yb(3+) , 2?%?Er(3+) in the luminescence imaging of cells was also investigated, which shows a bright-red emission without background noise.
HubMed – drug
HDAC3-selective inhibitor enhances extinction of cocaine-seeking behavior in a persistent manner.
Filed under: Drug and Alcohol Rehabilitation
Proc Natl Acad Sci U S A. 2013 Jan 7;
Malvaez M, McQuown SC, Rogge GA, Astarabadi M, Jacques V, Carreiro S, Rusche JR, Wood MA
Nonspecific histone deacetylase (HDAC) inhibition has been shown to facilitate the extinction of drug-seeking behavior in a manner resistant to reinstatement. A key open question is which specific HDAC is involved in the extinction of drug-seeking behavior. Using the selective HDAC3 inhibitor RGFP966, we investigated the role of HDAC3 in extinction and found that systemic treatment with RGFP966 facilitates extinction in mice in a manner resistant to reinstatement. We also investigated whether the facilitated extinction is related to the enhancement of extinction consolidation during extinction learning or to negative effects on performance or reconsolidation. These are key distinctions with regard to any compound being used to modulate extinction, because a more rapid decrease in a defined behavior is interpreted as facilitated extinction. Using an innovative combination of behavioral paradigms, we found that a single treatment of RGFP966 enhances extinction of a previously established cocaine-conditioned place preference, while simultaneously enhancing long-term object-location memory within subjects. During extinction consolidation, HDAC3 inhibition promotes a distinct pattern of histone acetylation linked to gene expression within the infralimbic cortex, hippocampus, and nucleus accumbens. Thus, the facilitated extinction of drug-seeking cannot be explained by adverse effects on performance. These results demonstrate that HDAC3 inhibition enhances the memory processes involved in extinction of drug-seeking behavior.
HubMed – drug
Modulating the innate immune response by combinatorial engineering of endotoxin.
Filed under: Drug and Alcohol Rehabilitation
Proc Natl Acad Sci U S A. 2013 Jan 7;
Needham BD, Carroll SM, Giles DK, Georgiou G, Whiteley M, Trent MS
Despite its highly inflammatory nature, LPS is a molecule with remarkable therapeutic potential. Lipid A is a glycolipid that serves as the hydrophobic anchor of LPS and constitutes a potent ligand of the Toll-like receptor (TLR)4/myeloid differentiation factor 2 receptor of the innate immune system. A less toxic mixture of monophosphorylated lipid A species (MPL) recently became the first new Food and Drug Administration-approved adjuvant in over 70 y. Whereas wild-type Escherichia coli LPS provokes strong inflammatory MyD88 (myeloid differentiation primary response gene 88)-mediated TLR4 signaling, MPL preferentially induces less inflammatory TRIF (TIR-domain-containing adaptor-inducing IFN-?)-mediated responses. Here, we developed a system for combinatorial structural diversification of E. coli lipid A, yielding a spectrum of bioactive variants that display distinct TLR4 agonist activities and cytokine induction. Mice immunized with engineered lipid A/antigen emulsions exhibited robust IgG titers, indicating the efficacy of these molecules as adjuvants. This approach demonstrates how combinatorial engineering of lipid A can be exploited to generate a spectrum of immunostimulatory molecules for vaccine and therapeutics development.
HubMed – drug
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