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1.
Int J Alzheimers Dis ; 20092010 Jan 27.
Article in English | MEDLINE | ID: mdl-20721294

ABSTRACT

Detecting aggregated amyloid peptides (Abeta plaques) presents targets for developing biomarkers of Alzheimer's disease (AD). Polymeric n-butyl-2-cyanoacrylate (PBCA) nanoparticles (NPs) were encapsulated with radiolabelled amyloid affinity (125)I-clioquinol (CQ, 5-chloro-7-iodo-8-hydroxyquinoline) as in vivo probes. (125)I-CQ-PBCA NPs crossed the BBB (2.3 +/- 0.9 ID/g) (P < .05) in the WT mouse (N = 210), compared to (125)I-CQ (1.0 +/- 0.4 ID/g). (125)I-CQ-PBCA NP brain uptake increased in AD transgenic mice (APP/PS1) versus WT (N = 38; 2.54 x 10(5) +/- 5.31 x 10(4) DLU/mm(2); versus 1.98 x 10(5) +/- 2.22 x 10(4) DLU/mm(2)) and in APP/PS1/Tau. Brain increases were in mice intracranially injected with aggregated Abeta(42) peptide (N = 17; 7.19 x 10(5) +/- 1.25 x 10(5) DLU/mm(2)), versus WT (6.07 x 10(5) +/- 7.47 x 10(4) DLU/mm(2)). Storage phosphor imaging and histopathological staining of the plaques, Fe(2+) and Cu(2+), validated results. (125)I-CQ-PBCA NPs have specificity for Abeta in vitro and in vivo and are promising as in vivo SPECT ((123)I), or PET ((124)I) amyloid imaging agents.

2.
Nanotechnology ; 21(3): 035101, 2010 Jan 22.
Article in English | MEDLINE | ID: mdl-19966403

ABSTRACT

Multi-color gold-nanoparticle-based tags (nanotags) are synthesized for combined surface-enhanced Raman spectroscopy (SERS) and x-ray computed tomography (CT). The nanotags are synthesized with quasi-spherical gold nanoparticles encoded with a reporter dye (color), each with a unique Raman spectrum. A library of nanotags with six different colors were synthesized for a range of gold nanoparticle sizes and an optimum size has been established to yield the largest SERS intensity and x-ray attenuation that is higher than the iodinated CT contrast agents used in clinics. Proof-of-principle in vivo imaging results with nanotags are presented that, for the first time, demonstrates the combined in vivo dual modality imaging capability of SERS and CT with a single nanoparticle probe.

3.
J Control Release ; 108(2-3): 193-214, 2005 Nov 28.
Article in English | MEDLINE | ID: mdl-16246446

ABSTRACT

Alzheimer's disease (AD) is the most common cause of dementia among the elderly, affecting 5% of Americans over age 65, and 20% over age 80. An excess of senile plaques (beta-amyloid protein) and neurofibrillary tangles (tau protein), ventricular enlargement, and cortical atrophy characterizes it. Unfortunately, targeted drug delivery to the central nervous system (CNS), for the therapeutic advancement of neurodegenerative disorders such as Alzheimer's, is complicated by restrictive mechanisms imposed at the blood-brain barrier (BBB). Opsonization by plasma proteins in the systemic circulation is an additional impediment to cerebral drug delivery. This review gives an account of the BBB and discusses the literature on biodegradable polymeric nanoparticles (NPs) with appropriate surface modifications that can deliver drugs of interest beyond the BBB for diagnostic and therapeutic applications in neurological disorders, such as AD. The physicochemical properties of the NPs at different surfactant concentrations, stabilizers, and amyloid-affinity agents could influence the transport mechanism.


Subject(s)
Alzheimer Disease/drug therapy , Blood-Brain Barrier/physiology , Drug Delivery Systems , Nanostructures , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Drug Compounding , Humans , Oxidative Stress , Pharmaceutical Preparations/metabolism , Polymers
4.
Transplantation ; 74(10): 1449-54, 2002 Nov 27.
Article in English | MEDLINE | ID: mdl-12451247

ABSTRACT

BACKGROUND: Natural killer (NK) cells use inhibitory Ly49 receptors to differentiate self from foreign cells based on interactions with major histocompatibility (MHC) class I molecules. Inhibitory receptors may recognize multiple MHC class I molecules. Studies to define ligands for the Ly49 receptors are complicated by the fact that receptors are expressed in overlapping subsets on NK cells. Binding studies can predict which MHC class I molecules are ligands for Ly49 receptors, but functional tests are required to substantiate results from binding studies. METHODS: We developed Ly49 receptor transgenic mice and studied the function of Ly49I(B6) in FVB.Ly49I(B6) transgenic mice using bone marrow transplantation assays to determine additional functional ligands for Ly49I(B6). We have also used fluorescence-activated cell sorting to isolate specific populations of B6 NK cells bearing Ly49I for use as effectors in chromium-release assays against a panel of Concanavalin A blast targets. RESULTS: Bone marrow transplantation studies indicate that H2-K(b), H2(s), and H2(v) serve as functional ligands for Ly49I(B6). In vitro cytotoxicity assays indicate that Ly49I recognizes H2(q), but not H2(d) or H2(k), target cells to inhibit NK killing. CONCLUSIONS: These data add support to previous binding studies by showing functional interactions between the B6-strain Ly49I and H2-K(b), H2(s), H2(v), and H2(q) class I antigens.


Subject(s)
Antigens, Ly/metabolism , H-2 Antigens/metabolism , Killer Cells, Natural/immunology , Animals , Bone Marrow Transplantation/immunology , Lectins, C-Type , Ligands , Mice , Mice, Transgenic , Receptors, NK Cell Lectin-Like
5.
J Immunol ; 169(7): 3661-6, 2002 Oct 01.
Article in English | MEDLINE | ID: mdl-12244158

ABSTRACT

Inhibitory Ly49 receptors expressed on NK cells provide a mechanism for tolerance to normal self tissues. The immunoregulatory tyrosine-based inhibitory motifs present in some Ly49s are able to transmit an inhibitory signal upon ligation by MHC class I ligands. In our system, as well as others, mice transgenic for inhibitory Ly49 receptors express these receptors on both NK and T cells. FVB (H2(q)) mice transgenic for the B6 strain Ly49I (Ly49I(B6)) express the inhibitory Ly49 receptor on the surface of both T and NK cells. Although Ly49I functions to prevent NK-mediated rejection of H2(b) donor bone marrow cells in this transgenic mouse strain, the T cells do not appear to be affected by the expression of the Ly49I transgene. FVB.Ly49I T cells have normal proliferative capabilities both in vitro and in vivo in response to the Ly49I ligand, H2(b). In vivo functional T cell assays were also done, showing that transgenic T cells were not functionally affected. T cells in these mice also appear to undergo normal T cell development and activation. Only upon stimulation with suboptimal doses of anti-CD3 in the presence of anti-Ly49I is T cell proliferation inhibited. These data are in contrast with findings in Ly49A, and Ly49G2 receptor transgenic models. Perhaps Ly49I-H2(b) interactions are weaker or of lower avidity than Ly49A-H-2D(d) interactions, especially in T cells.


Subject(s)
Antigens, Ly/biosynthesis , Antigens, Ly/genetics , Gene Expression Regulation/immunology , Receptors, Immunologic/biosynthesis , Receptors, Immunologic/genetics , Suppressor Factors, Immunologic/biosynthesis , Suppressor Factors, Immunologic/genetics , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Transgenes/immunology , Animals , Cell Differentiation/genetics , Cell Differentiation/immunology , Immunologic Memory/genetics , Immunophenotyping , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Lymphocyte Activation/genetics , Mice , Mice, Inbred C57BL , Mice, Inbred Strains , Mice, Transgenic , T-Lymphocyte Subsets/cytology
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