Engineered non-invasive functionalized dendrimer/dendron-entrapped/complexed gold nanoparticles as a novel class of theranostic (radio)pharmaceuticals in cancer therapy

Nanomedicine represents a very significant contribution in current cancer treatment; in addition to surgical intervention, radiation and chemotherapeutic agents that unfortunately also kill healthy cells, inducing highly deleterious and often life-threatening side effects in the patient. Of the numerous nanoparticles used against cancer, gold nanoparticles had been developed for therapeutic applications. Inter alia, a large variety of den drimers, i.e. soft artificial macromolecules, have turned up as non-viral functional nanocarriers for entrapping drugs, imaging agents, and targeting molecules. This review will provide insights into the design, synthesis, functionalization, and development in biomedicine of engineered functionalized hybrid dendrimer-tangled gold nanoparticles in the domain of cancer theranostic. Several aspects are highlighted and discussed such as 1) dendrimer-entrapped gold(0) hybrid nanoparticles for the targeted imaging and treatment of cancer cells, 2) dendrimer encapsulating gold(0) nanoparticles (Au DENPs) for the delivery of genes, 3) Au DENPs for drug delivery applications, 4) dendrimer encapsulating gold radioactive nanoparticles for radiotherapy, and 5) dendrimer/dendron-complexed gold(III) nanoparticles as technologies to take down cancer cells.info:eu-repo/semantics/publishedVersio

Dendrimers toward translational nanotherapeutics: concise key step analysis

The goal of nanomedicine is to address specific clinical problems optimally, to fight human diseases, and to find clinical relevance to change clinical practice. Nanomedicine is poised to revolutionize medicine via the development of more precise diagnostic and therapeutic tools. The field of nanomedicine encompasses numerous features and therapeutic disciplines. A plethora of nanomolecular structures have been engineered and developed for therapeutic applications based on their multitasking abilities and the wide functionalization of their core scaffolds and surface groups. Within nanoparticles used for nanomedicine, dendrimers as well polymers have demonstrated strong potential as nanocarriers, therapeutic agents, and imaging contrast agents. In this review, we present and discuss the different criteria and parameters to be addressed to prepare and develop druggable nanoparticles in general and dendrimers in particular. We also describe the major requirements, included in the preclinical and clinical roadmap, for NPs/dendrimers for the preclinical stage to commercialization. Ultimately, we raise the clinical translation of new nanomedicine issues.info:eu-repo/semantics/publishedVersio

Time-Dependent Subcellular Distribution and Effects of Carbon Nanotubes in Lungs of Mice

BACKGROUND AND METHODS:Pulmonary deposited carbon nanotubes (CNTs) are cleared very slowly from the lung, but there is limited information on how CNTs interact with the lung tissue over time. To address this, three different multiwalled CNTs were intratracheally instilled into female C57BL/6 mice: one short (850 nm) and tangled, and two longer (4 μm and 5.7 μm) and thicker. We assessed the cellular interaction with these CNTs using transmission electron microscopy (TEM) 1, 3 and 28 days after instillation. RESULTS:TEM analysis revealed that the three CNTs followed the same overall progression pattern over time. Initially, CNTs were taken up either by a diffusion mechanism or via endocytosis. Then CNTs were agglomerated in vesicles in macrophages. Lastly, at 28 days post-exposure, evidence suggesting CNT escape from vesicle enclosures were found. The longer and thicker CNTs more often perturbed and escaped vesicular enclosures in macrophages compared to the smaller CNTs. Bronchoalveolar lavage (BAL) showed that the CNT exposure induced both an eosinophil influx and also eosinophilic crystalline pneumonia. CONCLUSION:Two very different types of multiwalled CNTs had very similar pattern of cellular interactions in lung tissue, with the longer and thicker CNTs resulting in more severe effects in terms of eosinophil influx and incidence of eosinophilic crystalline pneumonia (ECP)

Time trends in leisure time physical activity and physical fitness in elderly people: 20 year follow-up of the Spanish population national health survey (1987-2006)

<p>Abstract</p> <p>Background</p> <p>To estimate trends in leisure time physical activity and physical fitness between 1987-2006 in older Spanish people.</p> <p>Methods</p> <p>We analyzed data collected from the Spanish National Health Surveys conducted in 1987 (n = 29,647), 1993 (n = 20,707), 1995-1997 (n = 12,800), 2001 (n = 21,058), 2003 (n = 21,650), and 2006 (n = 29,478). The number of subjects aged ≥ 65 years included in the current study was 29,263 (1987: n = 4,958-16.7%; 1993: n = 3,751-17.8%; 1995-97: n = 2,229-17.4%; 2001: n = 4,356-20.7%; 2003: 6,134-28.3%; 2006: 7,835-26.5%). Main variables included leisure-time physical activity and physical fitness. We analyzed socio-demographic characteristics, self-rated health status, lifestyle habit and co-morbid conditions using multivariate logistic regression models.</p> <p>Results</p> <p>Women exhibited lower prevalence of leisure time physical activity and physical fitness compared to men (P < 0.05). The multivariate analysis for time trends found that practising leisure time physical activity increased from 1987 to 2006 (P < 0.001). Variables associated with a lower likelihood of practicing leisure time physical activity were: age ≥ 80 years old, ≥ 2 co-morbid chronic conditions, and obesity. Variables associated with lower physical fitness included: age ≥ 80 years, worse self rated health; ≥ 2 medications (only for walking), and obesity.</p> <p>Conclusions</p> <p>We found an increase in leisure time physical activity in the older Spanish population. Older age, married status, co-morbid conditions, obesity, and worse self-perceived health status were associated with lower activity. Identification of these factors can help to identify individuals at risk for physical inactivity.</p

Evaluation of Amino-Functional Polyester Dendrimers Based on Bis-MPA as Nonviral Vectors for siRNA Delivery

Herein, we present the first evaluation of cationic dendrimers based on 2,2-bis(methylol)propionic acid (bis-MPA) as nonviral vectors for transfection of short interfering RNA (siRNA) in cell cultures. The study encompassed dendrimers of generation one to four (G1&ndash;G4), modified to bear 6&ndash;48 amino end-groups, where the G2&ndash;G4 proved to be capable of siRNA complexation and protection against RNase-mediated degradation. The dendrimers were nontoxic to astrocytes, glioma (C6), and glioblastoma (U87), while G3 and G4 exhibited concentration dependent toxicity towards primary neurons. The G2 showed no toxicity to primary neurons at any of the tested concentrations. Fluorescence microscopy experiments suggested that the dendrimers are highly efficient at endo-lysosomal escape since fluorescently labeled dendrimers were localized specifically in mitochondria, and diffuse cytosolic distribution of fluorescent siRNA complexed by dendrimers was observed. This is a desired feature for intracellular drug delivery, since the endocytic pathway otherwise transfers the drugs into lysosomes where they can be degraded without reaching their intended target. siRNA-transfection was successful in C6 and U87 cell lines using the G3 and G4 dendrimers followed by a decrease of approximately 20% of target protein p42-MAPK expression

Engineered non-invasive functionalized dendrimer/dendron-entrapped/complexed gold nanoparticles as a novel class of theranostic (radio)pharmaceuticals in cancer therapy

International audienceNanomedicine represents a very significant contribution in current cancer treatment; in addition to surgical intervention, radiation and chemotherapeutic agents that unfortunately also kill healthy cells, inducing highly deleterious and often life-threatening side effects in the patient. Of the numerous nanoparticles used against cancer, gold nanoparticles had been developed for therapeutic applications. Inter alia, a large variety of dendrimers, i.e. soft artificial macromolecules, have turned up as non-viral functional nanocarriers for entrapping drugs, imaging agents, and targeting molecules. This review will provide insights into the design, synthesis, functionalization, and development in biomedicine of engineered functionalized hybrid dendrimer-tangled gold nanoparticles in the domain of cancer theranostic. Several aspects are highlighted and discussed such as 1) dendrimer-entrapped gold(0) hybrid nanoparticles for the targeted imaging and treatment of cancer cells, 2) dendrimer encapsulating gold(0) nanoparticles (Au DENPs) for the delivery of genes, 3) Au DENPs for drug delivery applications, 4) dendrimer encapsulating gold radioactive nanoparticles for radiotherapy, and 5) dendrimer/dendron-complexed gold(III) nanoparticles as technologies to take down cancer cells

In vivo therapeutic applications of phosphorus dendrimers: state of the art

International audienceAmong the different types of dendrimers, those that incorporate phosphorus in various positions in their structures present fascinating properties and have wide applications in pharmaceutical fields such as drug delivery (including gene transfection), diagnosis and imaging. Therapeutic agents can be encapsulated within the dendritic architecture, or chemically attached or physically adsorbed onto the dendrimer surface. Alternatively, phosphorus dendrimers can be developed as drugs themselves, for instance to treat cancer, inflammations, infections and neurodegenerative diseases, although there are fewer examples of this second approach. Here, we review the most relevant in vivo biological activities of phosphorus dendrimers (whether as active drugs per se or as nanocarriers) across various therapeutic domains, including anti-inflammation, transmissible spongiform encephalopathies, ocular hypertension, infection, gene therapy, ultrasound-targeted microbubble destruction and two-photon in vivo imaging. We discuss the success of phosphorus dendrimers in nanomedicine and look ahead to future innovations in the field

Tricyclic antidepressants block cholinergic nicotinic receptors and ATP secretion in bovine chromaffin cells

Nicotine-induced ATP secretion from chromaffin cells was blocked by imipramine and desipramine. This blocking action took place on both, fast and slow, components of ATP secretion. Exposure of chromaffin cells to nicotine (10 microM) for 4 s induced an inward current of about -155 pA. Imipramine and desipramine blocked, in a concentration-dependent manner, both peak inward current and total charge influx in response to nicotine. In addition, imipramine and desipramine partially (40%) blocked depolarization-induced ATP secretion and Ca2+ currents evoked by high K+. This suggests that tricyclic antidepressants block nicotine-induced ATP secretion by acting on two targets: one is the nicotinic receptor itself and the second one are voltage-dependent Ca2+ channels.This work has been supported in part by grants from Fondo de Investigaciones Sanitarias (95/1655) to C.G.G.; from DGICYT (PM92-0112), Comision Interministerial de Ciencia y Tecnologia, Plan Nacional de Salud (SAF96-0169) and Fundacion Navarro-Tripodi to V.C

omega-Agatoxin IVA blocks nicotinic receptor channels in bovine chromaffin cells

We have studied the contribution of P-type voltage-dependent Ca2+ channels to both catacholamine (CA) and ATP secretion from bovine chromaffin cells induced by high K+ or nicotine using omega-agatoxin IVA, a selective blocker of P-type voltage-dependent Ca2+ channels. We found that high K+ (75 mM) induced the release of about 13% of norepinephrine, 5% epinephrine and 11% ATP, and that omega-agatoxin (100 nM) did not affect this secretion. However, both nicotine-induced CA and ATP secretion were significantly blocked (about 50%) by omega-agatoxin IVA (100 nM). In addition, this toxin also reversibly blocked (about 70%) the inward current induced by nicotine in bovine chromaffin cells. The results suggest that, besides its known action of blocking P-type voltage-dependent channels, omega-agatoxin is a potent and reversible blocker of the nicotinic receptor channel in chromaffin cells, and that this action would explain the blockade of nicotine-induced secretion.This work was supported, in part, by grants from Fundación Salud 2000, Dirección General de Investigación Cientifica y Técnica, Grant PM92-0112, and the European Economic Community, Grant SC1"-CT91-0709. R.G. was supported by a University of Alicante fellowship, J.M.F. by a CAM fellowship, and V.I. by a Generalitat Valenciana fellowship