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Functionalized carbon nanotubes as emerging nanovectors for the delivery of therapeutics
- Biochim. Biophys. Acta 2006
"... Abstract Functionalized carbon nanotubes ( f-CNT) are emerging as a new family of nanovectors for the delivery of different types of therapeutic molecules. The application of CNT in the field of carrier-mediated delivery has become possible after the recent discovery of their capacity to penetrate ..."
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Abstract Functionalized carbon nanotubes ( f-CNT) are emerging as a new family of nanovectors for the delivery of different types of therapeutic molecules. The application of CNT in the field of carrier-mediated delivery has become possible after the recent discovery of their capacity to penetrate into the cells. CNT can be loaded with active molecules by forming stable covalent bonds or supramolecular assemblies based on noncovalent interactions. Once the cargos are carried into various cells, tissues and organs they are able to express their biological function. In this review, we will describe the potential of f-CNT to deliver different types of therapeutic molecules. D
Complement activation by bisretinoid constituents of RPE lipofuscin.
- Invest. Ophthalmol. Vis. Sci.
, 2009
"... PURPOSE. Studies implicate activation of complement among the processes involved in the pathogenesis of age-related macular degeneration (AMD). Questions pertain to the trigger(s) responsible for the complement-associated events. The authors previously reported that photooxidation products of A2E c ..."
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PURPOSE. Studies implicate activation of complement among the processes involved in the pathogenesis of age-related macular degeneration (AMD). Questions pertain to the trigger(s) responsible for the complement-associated events. The authors previously reported that photooxidation products of A2E can activate complement. Here they have further explored these events. METHODS. In vitro assays using human serum as a source of complement were used, and the C3 split product iC3b was measured by enzyme immunoassay. Serum was placed in contact with ARPE-19 cells and polarized human fetal retinal pigment epithelium that had accumulated A2E and were irradiated (430 nm). Serum was also incubated in wells precoated with bisretinoid pigments of lipofuscin and their oxidized forms. iC3b generation in normal human serum (NHS) was compared with that in factor B-depleted and C1q-depleted human serum. RESULTS. iC3b levels were elevated in NHS placed in contact with A2E-laden retinal pigment epithelium that were irradiated to generate A2E photooxidation products. iC3b was also increased in serum incubated in wells precoated with peroxy-A2E, the lipofuscin pigment all-trans-retinal dimer, and oxidized forms of all-trans-retinal dimer. Substitution of NHS with factor B-depleted sera abrogated these increases in iC3b. Complement activation was also suppressed by the addition of C-reactive protein and by a C3 cleavage inhibitor. CONCLUSIONS. The authors suggest that bisretinoid pigments of retinal pigment epithelial lipofuscin, subsequent to photoactivation and cleavage, serve to activate complement. Complement activation by this mechanism is dependent on the alternative pathway and can be modulated by an inhibitor of C3 cleavage. These events in the setting of complement dysregulation could contribute to the chronic inflammation that underlies AMD pathogenesis. (Invest Ophthalmol Vis Sci. 2009; 50:1392-1399 DOI:10.1167DOI:10. /iovs.08-2868 L inks between the complement system, an arm of innate immunity, and age-related macular degeneration (AMD) have been provided by analyses of the composition of the extracellular deposits that form subretinally as drusen 1-4 and by molecular genetic studies. 16 Although several haplotypes of the CFH gene are associated with either increased or decreased susceptibility to AMD, 8 the most studied is the Y402H variant. Longitudinal prospective population-based studies with the power to determine the magnitude of the role played by CFH have confirmed the highly significant association between the CFH 402H polymorphism (genotype 1277CC) and risk for AMD. 19 Population-attributable risk for late AMD was estimated to be 54% in the presence of 1 allele or 2 alleles. Prompted by an interest in identifying mechanisms linking factors implicated in AMD pathogenesis, including inflammation, oxidative damage, drusen, and retinal pigment epithelial (RPE) lipofuscin, we previously explored the possibility that products of the photooxidation of RPE lipofuscin pigments activate the complement system. 21-24 These lipofuscin constituents are photoreactive molecules that absorb light in the visible range of the spectrum, generate reactive forms of oxygen, become oxidized, and undergo photo-induced fragmentation. 29 Mono-and bis-oxygenated photoproducts of A2E and all-trans-retinal dimer (furano-A2E, peroxy-A2E, furano-all-trans-retinal dimer, peroxy-all-trans-retinal dimer) have also been identified.
Higher dispersion efficacy of functionalized carbon nanotubes in chemical and biological environments
- ACS Nano
"... ABSTRACT Aqueous dispersions of functionalized carbon nanotubes (CNTs) are now widely used for biomedical applications. Their stability in different in vitro or in vivo environments, however, depends on a wide range of parameters, such as pH and salt concentrations of the 2 surrounding medium, and l ..."
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ABSTRACT Aqueous dispersions of functionalized carbon nanotubes (CNTs) are now widely used for biomedical applications. Their stability in different in vitro or in vivo environments, however, depends on a wide range of parameters, such as pH and salt concentrations of the 2 surrounding medium, and length, aspect ratio, surface charge and functionalization of the applied CNTs. Although many of these aspects have been investigated separately, no study is available in the literature to date, which examines these parameters simultaneously. Therefore, we have chosen five types of carbon nanotubes, varying in their dimensions and surface properties, for a multi-dimensional analysis of dispersion stability in salt solutions of differing pH and concentrations. Furthermore, we examine the dispersion stability of oxidised CNTs in biological fluids, such as cellular growth media and human plasma, and their toxicity towards cancer cells. To enhance dispersability and biocompatibility, the influence of different functionalization schemes is studied. The results of our investigations indicate that both CNT dimensions and surface functionalization have a significant influence on their dispersion and in vitro behavior. In particular, factors such as a short aspect ratio, presence of oxidation debris and serum proteins,
Farokhzad, Immunocompatibility properties of lipid– polymer hybrid nanoparticles with heterogeneous surface functional groups
- Biomaterials
"... a b s t r a c t Here we report the immunological characterization of lipid-polymer hybrid nanoparticles (NPs) and propose a method to control the levels of complement activation induced by these NPs. This method consists of the highly specific modification of the NP surface with methoxyl, carboxyl, ..."
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a b s t r a c t Here we report the immunological characterization of lipid-polymer hybrid nanoparticles (NPs) and propose a method to control the levels of complement activation induced by these NPs. This method consists of the highly specific modification of the NP surface with methoxyl, carboxyl, and amine groups. Hybrid NPs with methoxyl surface groups induced the lowest complement activation, whereas the NPs with amine surface groups induced the highest activation. All possible combinations among carboxyl, amine, and methoxyl groups also activated the complement system to a certain extent. All types of NPs activated the complement system primarily via the alternative pathway rather than the lectin pathway. The classical pathway was activated to a very small extent by the NPs with carboxyl and amine surface groups. Human serum and plasma protein binding studies showed that these NPs had different protein binding patterns. Studies of both complement activation and coagulation activation suggested that NPs with methoxyl surface groups might be an ideal candidate for drug delivery applications, since they are not likely to cause any immunological adverse reaction in the human body. Published by Elsevier Ltd.
Purification and characterisation of immunoglobulins from the Australian black flying fox (Pteropus alecto) using anti-fab affinity chromatography reveals the low abundance of IgA
- PLOS ONE
"... There is now an overwhelming body of evidence that implicates bats in the dissemination of a long list of emerging and re-emerging viral agents, often causing illnesses or death in both animals and humans. Despite this, there is a paucity of information regarding the immunological mechanisms by whic ..."
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There is now an overwhelming body of evidence that implicates bats in the dissemination of a long list of emerging and re-emerging viral agents, often causing illnesses or death in both animals and humans. Despite this, there is a paucity of information regarding the immunological mechanisms by which bats coexist with highly pathogenic viruses. Immunoglobulins are major components of the adaptive immune system. Early studies found bats may have quantitatively lower antibody responses to model antigens compared to conventional laboratory animals. To further understand the antibody response of bats, the present study purified and characterised the major immunoglobulin classes from healthy black flying foxes, Pteropus alecto. We employed a novel strategy, where IgG was initially purified and used to generate anti-Fab specific antibodies. Immobilised anti-Fab specific antibodies were then used to capture other immunoglobulins from IgG depleted serum. While high quantities of IgM were successfully isolated from serum, IgA was not. Only trace quantities of IgA were detected in the serum by mass spectrometry. Immobilised ligands specific to IgA (Jacalin, Peptide M and staphylococcal superantigen-like protein) also failed to capture P. alecto IgA from serum. IgM was the second most abundant serum antibody after IgG. A survey of mucosal secretions found IgG was the dominant antibody class rather than IgA. Our study demonstrates healthy P. alecto bats have markedly less serum IgA than expected. Higher quantities of IgG in mucosal secretions may be compensation for this low abundance or lack of IgA. Knowledge and reagents developed within
Effects of long and short carboxylated or aminated multiwalled carbon nanotubes on blood coagulation. PLoS One 7: e38995. doi: 10.1371/journal.pone.0038995. PMID
, 2012
"... In this work the effects of four different multiwalled carbon nanotubes (MWCNTs), including long carboxylated (L-COOH), short carboxylated (S-COOH), long aminated (L-NH2) and short aminated (S-NH2) ones, on the integrity of red blood cells, coagulation kinetics and activation of platelets were inves ..."
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In this work the effects of four different multiwalled carbon nanotubes (MWCNTs), including long carboxylated (L-COOH), short carboxylated (S-COOH), long aminated (L-NH2) and short aminated (S-NH2) ones, on the integrity of red blood cells, coagulation kinetics and activation of platelets were investigated with human whole blood. We found that the four MWCNTs induced different degrees of red blood cell damage as well as a mild level of platelet activation (10–25%). L-COOH and L-NH2 induced a higher level of platelet activation than S-COOH and S-NH2 respectively; meanwhile L-NH2 caused marked reductions in platelet viability. The presence of the four MWCNTs led to earlier fibrin formation, L-NH2 increased the clots hardness significantly, while L-COOH and S-NH2 made the clots become softer. It was concluded that the four MWCNTs affected blood coagulation process and the clots mechanical properties; they also altered the integrity of the red blood cells and the viability of the platelets, as well as induced platelets activation. The effects of MWCNTs depended on the size and chemistry of the nanotubes and the type of cells they contacted.
Bibliothèque et Archives nationales
"... Robert-Sauvé en santé et en sécurité du travail (IRSST) is a scientific research organization known for the quality of its work and the expertise of its personnel. OUR RESEARCH is working for you! Mission To contribute, through research, to the prevention of industrial accidents and occupational dis ..."
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Robert-Sauvé en santé et en sécurité du travail (IRSST) is a scientific research organization known for the quality of its work and the expertise of its personnel. OUR RESEARCH is working for you! Mission To contribute, through research, to the prevention of industrial accidents and occupational diseases as well as to the rehabilitation of affected workers. To offer the laboratory services and expertise necessary for the activities of the public occupational health and safety prevention network. To disseminate knowledge, and to act as scientific benchmark and expert. Funded by the Commission de la santé et de la sécurité du travail, the IRSST has a board of directors made up of an equal number of employer and worker representatives. To find out more Visit our Web site for complete up-to-date information about the IRSST. All our publications can be downloaded at no charge. www.irsst.qc.ca To obtain the latest information on the research carried out or funded by the IRSST, subscribe to Prévention au travail, the free magazine published jointly by the IRSST and the CSST.
unknown title
, 2006
"... www.elsevier.com/locate/carbon Binding of pulmonary surfactant proteins to carbon nanotubes; potential for damage to lung immune defense mechanisms ..."
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www.elsevier.com/locate/carbon Binding of pulmonary surfactant proteins to carbon nanotubes; potential for damage to lung immune defense mechanisms