318 research outputs found
Biocompatible Nanocomplexes for Molecular Targeted MRI Contrast Agent
Accurate diagnosis in early stage is vital for the treatment of Hepatocellular carcinoma. The aim of this study was to investigate the potential of poly lactic acidâpolyethylene glycol/gadoliniumâdiethylenetriamine-pentaacetic acid (PLAâPEG/GdâDTPA) nanocomplexes using as biocompatible molecular magnetic resonance imaging (MRI) contrast agent. The PLAâPEG/GdâDTPA nanocomplexes were obtained using self-assembly nanotechnology by incubation of PLAâPEG nanoparticles and the commercial contrast agent, GdâDTPA. The physicochemical properties of nanocomplexes were measured by atomic force microscopy and photon correlation spectroscopy. The T1-weighted MR images of the nanocomplexes were obtained in a 3.0 T clinical MR imager. The stability study was carried out in human plasma and the distribution in vivo was investigated in rats. The mean size of the PLAâPEG/GdâDTPA nanocomplexes was 187.9 ± 2.30 nm, and the polydispersity index was 0.108, and the zeta potential was â12.36 ± 3.58 mV. The results of MRI test confirmed that the PLAâPEG/GdâDTPA nanocomplexes possessed the ability of MRI, and the direct correlation between the MRI imaging intensities and the nano-complex concentrations was observed (r = 0.987). The signal intensity was still stable within 2 h after incubation of the nanocomplexes in human plasma. The nanocomplexes gave much better image contrast effects and longer stagnation time than that of commercial contrast agent in rat liver. A dose of 0.04 mmol of gadolinium per kilogram of body weight was sufficient to increase the MRI imaging intensities in rat livers by five-fold compared with the commercial GdâDTPA. PLAâPEG/GdâDTPA nanocomplexes could be prepared easily with small particle sizes. The nanocomplexes had high plasma stability, better image contrast effect, and liver targeting property. These results indicated that the PLAâPEG/GdâDTPA nanocomplexes might be potential as molecular targeted imaging contrast agent
Synthesis of Fluorine-18 Functionalized Nanoparticles for use as in vivo Molecular Imaging Agents
Nanoparticles containing fluorine-18 were prepared from block copolymers made by ring opening metathesis polymerization (ROMP). Using the fast initiating ruthenium metathesis catalyst (H_2IMes)(pyr)_2(Cl)_2Ru=CHPh, low polydispersity amphiphilic block copolymers were prepared from a cinnamoyl-containing hydrophobic norbornene monomer and a mesyl-terminated PEG-containing hydrophilic norbornene monomer. Self-assembly into micelles and subsequent cross-linking of the micelle cores by light-activated dimerization of the cinnamoyl groups yielded stable nanoparticles. Incorporation of fluorine-18 was achieved by nucleophilic displacement of the mesylates by the radioactive fluoride ion with 31% incorporation of radioactivity. The resulting positron-emitting nanoparticles are to be used as in vivo molecular imaging agents for use in tumor imaging
A Novel Docetaxel-Loaded Poly (Δ-Caprolactone)/Pluronic F68 Nanoparticle Overcoming Multidrug Resistance for Breast Cancer Treatment
Multidrug resistance (MDR) in tumor cells is a significant obstacle to the success of chemotherapy in many cancers. The purpose of this research is to test the possibility of docetaxel-loaded poly (Δ-caprolactone)/Pluronic F68 (PCL/Pluronic F68) nanoparticles to overcome MDR in docetaxel-resistance human breast cancer cell line. Docetaxel-loaded nanoparticles were prepared by modified solvent displacement method using commercial PCL and self-synthesized PCL/Pluronic F68, respectively. PCL/Pluronic F68 nanoparticles were found to be of spherical shape with a rough and porous surface. The nanoparticles had an average size of around 200 nm with a narrow size distribution. The in vitro drug release profile of both nanoparticle formulations showed a biphasic release pattern. There was an increased level of uptake of PCL/Pluronic F68 nanoparticles in docetaxel-resistance human breast cancer cell line, MCF-7 TAX30, when compared with PCL nanoparticles. The cytotoxicity of PCL nanoparticles was higher than commercial TaxotereŸin the MCF-7 TAX30 cell culture, but the differences were not significant (p > 0.05). However, the PCL/Pluronic F68 nanoparticles achieved significantly higher level of cytotoxicity than both of PCL nanoparticles and TaxotereŸ(p < 0.05), indicating docetaxel-loaded PCL/Pluronic F68 nanoparticles could overcome multidrug resistance in human breast cancer cells and therefore have considerable potential for treatment of breast cancer
Nanoparticles that communicate in vivo to amplify tumour targeting
Author Manuscript: 2012 May 29Nanomedicines have enormous potential to improve the precision of cancer therapy, yet our ability to efficiently home these materials to regions of disease in vivo remains very limited. Inspired by the ability of communication to improve targeting in biological systems, such as inflammatory-cell recruitment to sites of disease, we construct systems where synthetic biological and nanotechnological components communicate to amplify disease targeting in vivo. These systems are composed of âsignallingâ modules (nanoparticles or engineered proteins) that target tumours and then locally activate the coagulation cascade to broadcast tumour location to clot-targeted âreceivingâ nanoparticles in circulation that carry a diagnostic or therapeutic cargo, thereby amplifying their delivery. We show that communicating nanoparticle systems can be composed of multiple types of signalling and receiving modules, can transmit information through multiple molecular pathways in coagulation, can operate autonomously and can target over 40 times higher doses of chemotherapeutics to tumours than non-communicating controls.National Cancer Institute (U.S.) (SBMRI Cancer Center Support Grant 5 P30 CA30199-28)National Cancer Institute (U.S.) (MIT CCNE Grant U54 CA119349)National Cancer Institute (U.S.) (Bioengineering Research Partnership Grant 5-R01-CA124427)National Cancer Institute (U.S.) (UCSD CCNE Grant U54 CA 119335)National Science Foundation (U.S.) (Whitaker Graduate Fellowship
Genome-Wide Interaction Analysis of Air Pollution Exposure and Childhood Asthma with Functional Follow-up
Rationale: The evidence supporting an association between traffic-related air pollution exposure and incident childhood asthma is inconsistent and may depend on genetic factors. Objectives: To identify geneâenvironment interaction effects on childhood asthma using genome-wide single-nucleotide polymorphism (SNP) data and air pollution exposure. Identified loci were further analyzed at epigenetic and transcriptomic levels. Methods: We used land use regression models to estimate individual air pollution exposure (represented by outdoor NO2 levels) at the birth address and performed a genome-wide interaction study for doctorsâ diagnoses of asthma up to 8 years in three European birth cohorts (nâ=â1,534) with look-up for interaction in two separate North American cohorts, CHS (Childrenâs Health Study) and CAPPS/SAGE (Canadian Asthma Primary Prevention Study/Study of Asthma, Genetics and Environment) (nâ=â1,602 and 186 subjects, respectively). We assessed expression quantitative trait locus effects in human lung specimens and blood, as well as associations among air pollution exposure, methylation, and transcriptomic patterns. Measurements and Main Results: In the European cohorts, 186 SNPs had an interaction Pâ<â1âĂâ10â4 and a look-up evaluation of these disclosed 8 SNPs in 4 loci, with an interaction Pâ<â0.05 in the large CHS study, but not in CAPPS/SAGE. Three SNPs within adenylate cyclase 2 (ADCY2) showed the same direction of the interaction effect and were found to influence ADCY2 gene expression in peripheral blood (Pâ=â4.50âĂâ10â4). One other SNP with Pâ<â0.05 for interaction in CHS, rs686237, strongly influenced UDP-Gal:betaGlcNAc ÎČ-1,4-galactosyltransferase, polypeptide 5 (B4GALT5) expression in lung tissue (Pâ=â1.18âĂâ10â17). Air pollution exposure was associated with differential discs, large homolog 2 (DLG2) methylation and expression. Conclusions: Our results indicated that geneâenvironment interactions are important for asthma development and provided supportive evidence for interaction with air pollution for ADCY2, B4GALT5, and DLG2
Gaussian Process-based prediction of memory performance and biomarker status in ageing and Alzheimer's disease-A systematic model evaluation
Neuroimaging markers based on Magnetic Resonance Imaging (MRI) combined with various other measures (such as genetic covariates, biomarkers, vascular risk factors, neuropsychological tests etc.) might provide useful predictions of clinical outcomes during the progression towards Alzheimer's disease (AD). The use of multiple features in predictive frameworks for clinical outcomes has become increasingly prevalent in AD research. However, many studies do not focus on systematically and accurately evaluating combinations of multiple input features. Hence, the aim of the present work is to explore and assess optimal combinations of various features for MR-based prediction of (1) cognitive status and (2) biomarker positivity with a multi kernel learning Gaussian process framework. The explored features and parameters included (A) combinations of brain tissues, modulation, smoothing, and image resolution;(B) incorporating demographics & clinical covariates;(C) the impact of the size of the training data set;(D) the influence of dimensionality reduction and the choice of kernel types. The approach was tested in a large German cohort including 959 subjects from the multicentric longitudinal study of cognitive impairment and dementia (DELCODE). Our evaluation suggests the best prediction of memory performance was obtained for a combination of neuroimaging markers, demographics, genetic information (ApoE4) and CSF biomarkers explaining 57% of outcome variance in out-of sample predictions. The highest performance for A 42/40 status classification was achieved for a combination of demographics, ApoE4, and a memory score while usage of structural MRI further improved the classification of individual patient's pTau status
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PEGylated systems in pharmaceutics
This review addresses the use of poly(ethylene glycol) (PEG) and PEG conjugation for the design of novel dosage forms and the modification of biomolecules. The peculiarities of PEGylated nanoparticles, liposomes, proteins, enzymes, and small drug and polyelectrolyte molecules and their influence on systemic drug delivery, including overcoming of various biological barriers and adhesion to mucosal tissues (mucoadhesion), are considered
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