Candidates For Carriers Research Articles

Swelling/deswelling, thermal, and rheological behavior of PVA-g-NIPAAm nanohydrogels prepared by a facile free-radical polymerization method

A novel method of synthesizing poly(vinyl alcohol)-g-N-isopropylacrylamide (PVA-g-NIPAAm) nanohydrogels under crosslinker-free conditions at high dilution and elevated temperature is presented. Hydrogen peroxide (H2O2), used as an initiator, decomposes to hydroxyl radicals at high temperature, which causes the abstraction of hydrogen from PVA chains, resulting in NIPAAm-grafting polymerization. Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA) confirmed the grafting polymerization of NIPAAm onto PVA chains. The effects of the NIPAAm/PVA feed composition ratio, the amount of H2O2, and both pH and temperature on the swelling properties of the nanohydrogels obtained were investigated. An investigation of the swelling/deswelling kinetics and oscillatory swelling behavior of the nanohydrogels indicated that they have high swelling ratios with fast response rates and good reversibilities, and are sensitive to both pH and temperature. Elemental analysis revealed that the NIPAAm content increases with increasing NIPAAm/PVA ratio and H2O2 concentration, which leads to a remarkable increase in the nanohydrogel swelling ratio. Rheological studies demonstrated that the samples with higher PVA contents had enhanced elastic responses. The phase-transition temperatures and size distributions of the nanohydrogels were also studied. It appears that that these fast-responding nanohydrogels with properties that are sensitive to both pH and temperature, and which are obtained by a relatively simple and convenient polymerization method, could be potential candidates for drug-delivery carriers.

A Blind 3D Watermarking Approach for 3D Mesh Using Clustering Based Methods

Blind and robust watermarking of 3D mesh aims to embed message into a 3D mesh model such that the mesh is not visually distorted from the original model. An essential condition is that the message should be securely extracted even after the mesh model was processed. This paper explores use of artificial intelligence techniques to build blind and robust 3D-watermarking approach. It is based on clustering 3D vertices into appropriate or inappropriate candidates for watermark insertion using K-means clustering and Self Organization Map (SOM) clustering algorithms. The watermark insertion were performed only on set of selected vertices come out from clustering technique. These vertices are used as candidates for watermark carriers that will hold watermark bits stream. Through the simulations, the authors prove that the proposed approach is robust against various kinds of geometrical attacks such as mesh smoothing, noise addition and mesh cropping.

Fluorescent organic nanoparticles self-assembled from hexa[p-(carbonyl glycin methyl ester) phenoxy] cyclotriphosphazene in solution

Novel organic nanoparticles self-assembled from the hexa[p-(carbonyl glycin methyl ester) phenoxy] cyclotriphosphazene (HGPCP) were prepared by a simple solution method. The as-prepared nanoparticles were extensively characterized by SEM, TEM, XRD, TGA, and fluorescence spectrum. The size of nanoparticles was increased with increasing the HGPCP concentration in solution. The effect of reaction conditions on the particle size and stability was further investigated. Based upon the experimental results, a growth mechanism was proposed for the formation of the nanoparticles. The obtained nanoparticles were highly thermal stable and exhibited strong fluorescent emission, which could be potential candidates for drug-loading carriers and tracer drug delivery.

Self-assembly of nanoparticles from cyclotriphosphazenes grafted with hexa-[p-(carbonyl tryptophan ethyl ester) phenoxy)] group

A new cyclotriphosphazene derivative substituted by tryptophan ethyl ester groups, namely, hexa-[p-(carbonyl tryptophan ethyl ester) phenoxy)] cyclotriphosphazene (HEPCP), was synthesized. The nanoparticles self-assembled from the hydrophobic HEPCP were prepared by a facile desolvation method. The nanoparticles were characterized by SEM, TEM, FTIR, XRD, TGA, CLSM and fluorescence spectrum. Based upon the molecular conformation of HEPCP and the spatial arrangements of side substituent groups, a growth mechanism was proposed for the formation of the nanoparticles. The obtained nanoparticles were highly thermally stable and exhibited strong fluorescent emission, and could be potential candidates for drug-loading carriers and tracer drug delivery.

Calcium condensed cell penetrating peptide complexes offer highly efficient, low toxicity gene silencing

The development of short-interfering RNA (siRNA) offers new strategies for manipulating specific genes responsible for pathological disorders. Myriad cationic polymer and lipid formulations have been explored, but an effective, non-toxic carrier remains a major barrier to clinical translation. Among the emerging candidates for siRNA carriers are cell penetrating peptides (CPPs), which can traverse the plasma membrane and facilitate the intracellular delivery of siRNA. Previously, a highly efficient and non-cytotoxic means of gene delivery was designed by complexing plasmid DNA with CPPs, then condensing with calcium. Here, the CPP TAT and a longer, ‘double’ TAT (dTAT) were investigated as potential carriers for siRNA. Various N/P ratios and calcium concentrations were used to optimize siRNA complexes in vitro. Upon addition of calcium, ‘loose’ siRNA/CPP complexes were condensed into small nanoparticles. Knockdown of luciferase expression in the human epithelial lung cell line A549-luc-C8 was high (up to 93%) with no evidence of cytotoxicity. Selected formulations of the dTAT complexes were dosed intravenously up to 1000mg/kg with minimal toxicity. Biodistribution studies revealed high levels of gene knockdown in the lung and muscle tissue suggesting these simple vectors may offer a translatable approach to siRNA delivery.

Synthesis and characterization of pore size-tunable magnetic mesoporous silica nanoparticles

Magnetic mesoporous silica nanoparticles (M-MSNs) are emerging as one of the most appealing candidates for theranostic carriers. Herein, a simple synthesis method of M-MSNs with a single Fe3O4 nanocrystal core and a mesoporous shell with radially aligned pores was elaborated using tetraethyl orthosilicate (TEOS) as silica source, cationic surfactant CTAB as template, and 1,3,5-triisopropylbenzene (TMB)/decane as pore swelling agents. Due to the special localization of TMB during the synthesis process, the pore size was increased with added TMB amount within a limited range, while further employment of TMB lead to severe particle coalescence and not well-developed pore structure. On the other hand, when a proper amount of decane was jointly incorporated with limited amounts of TMB, effective pore expansion of M-MSNs similar to that of analogous mesoporous silica nanoparticles was realized. The resultant M-MSN materials possessed smaller particle size (about 40–70nm in diameter), tunable pore sizes (3.8–6.1nm), high surface areas (700–1100m2/g), and large pore volumes (0.44–1.54cm3/g). We also demonstrate their high potential in conventional DNA loading. Maximum loading capacity of salmon sperm DNA (375mg/g) was obtained by the use of the M-MSN sample with the largest pore size of 6.1nm.

Influence of the block hydrophilicity of AB2 miktoarm star copolymers on cluster formation in solutions

We investigated the formation of various micelle shapes of lipid-like amphiphilic AB(2) miktoarm star copolymers in a solution, by performing dissipative particle dynamics simulations. AB(2) miktoarm star copolymer molecules are modeled with coarse-grained structures that consist of a relatively hydrophilic head (A) group with a single arm and a hydrophobic tail (B) group with double arms. A decrease in the hydrophilicity of the head group leads to a reduction of the polymer-solvent contact area, causing cluster structure changes from spherical micelles to vesicles. Consequently, a spherical exterior with multi-lamellar or cylindrical phase interior structures forms under poor solvent conditions without the introduction of spherical hard-wall containers. Furthermore we observed that, for small head group lengths, vesicles were formed in much wider range of solvent-head interaction strength than for long head groups, indicating that molecules with short head group offer a superior vesicle forming property. A phase diagram, the structure and kinetics of the cluster formation, a density profile, and a detailed shape analysis are presented to discuss the molecular characteristics of potential candidates for drug carriers that require superior and versatile vesicle forming properties. We also show that, under certain solvent-hydrophilic head group interaction conditions, initially formed cylindrical micelles transform to bilayer fragments through redistribution of copolymers within the cluster.

ELECTRONIC ABSORPTION SPECTRA OF PROTONATED ANTHRACENES AND PHENANTHRENES, AND THEIR NEUTRALS IN NEON MATRICES

Electronic spectra of three isomers of protonated anthracene and five isomers of protonated phenanthrene have been detected in 6 K neon matrices following deposition of mass-selected m/z = 179 cations produced from dihydro-anthracene or -phenanthrene. The cations exhibit moderately intense band systems in the 400-550 nm range. Corresponding neutrals have been observed in the UV. The absorptions are assigned to specific isomers of the protonated species on the basis of time-dependent density functional theory calculations. The astrophysical relevance of protonated anthracenes and phenanthrenes as candidates for carriers of diffuse interstellar bands is discussed.

Amphiphilic CCK peptides assembled in supramolecular aggregates: structural investigations and in vitro studies

Supramolecular aggregates obtained by self-aggregation of five new cationic amphiphilic CCK8 peptides have been obtained in water solution and characterized for: (i) aggregate structure and stability; (ii) CCK8 peptide conformation and bioavailability on the external aggregate surface; and (iii) for their cell binding properties. The cationic amphiphilic CCK8 peptides self-aggregate giving a combination of liposomal and micelle structures, with radii ranging between ~60 nm and ~90 nm, and between ~5 and ~10 nm, respectively. The presence of CCK8 peptide well-exposed on the aggregate surface is demonstrated by fluorescence measurements. Peptide conformation changes in the five supramolecular aggregates: the CCK8 conformational behaviour is probably induced by the presence of three charged lysine residues close to the bioactive peptide sequence. Only aggregates in which the CCK8 peptide presents a structural arrangement similar to that found for the same peptide in DPC micelles give promising binding properties to CCK2-R receptors overexpressed by transfected A431 cells. Chemical modifications on the CCK8 N-terminus seem to play an important role in stabilizing the peptide active conformation, either when the peptide derivative is in monomeric or in aggregate form. For their easy preparation procedures and their binding properties, supramolecular aggregates based on cationic peptide amphiphiles can be considered as promising candidates for target selective drug carriers on cancer cells.

Towards biocompatible nanovalves based on mesoporous silica nanoparticles

Over the past two decades, cancer has ascended to become the number one or two cause of death in many nations worldwide. Encapsulation of anticancer drugs within nanocarriers that selectively target diseased cells promises to increase the effectiveness of conventional chemotherapy and decrease its side effects. Nanoparticles show great potential as superior intelligent drug delivery platforms. Among them, mesoporous silica nanoparticles (MSNs) are particularly interesting candidates for powerful drug carriers because of their unique characteristics and abilities to efficiently and specifically entrap cargo molecules. The biggest challenge in current development is the design and synthesis of controlled biocompatible nanovalves or cap systems on MSNs to realize “zero premature release” of drugs and targeted delivery of anticancer drugs in a controlled fashion for “smart” cancer therapies. This review article evaluates drug delivery systems which comprise MSNs functionalized with well-defined self-assembled layers of biocompatible molecular and supramolecular nanovalves based on (supra)molecular switches, polymers, and biomolecules. Recent research progress on MSN-based smart materials that can simultaneously address targeted delivery of anticancer drugs, ideally “zero premature release”, and controlled release by external physical, chemical and biological stimuli will be highlighted and discussed.

Solvent-controlled self-assembly of amphiphilic cholic acid-modified PAMAM dendrimers

Here we present the special self-assembly properties of the amphiphilic macromolecules made from G1 PAMAM dendrimers partially modified with cholic acid. These cholic acid-derived macromolecules can self-assemble in both apolar and polar solvents. The aggregates of these macromolecules in toluene can partially extract hydrophilic molecules from water to toluene. The macromolecules in aqueous solutions can form multiple morphological aggregates which are nanoparticles below pH 10.0 and microparticles above pH 13.0. The nanoparticles release methotrexate, an anticancer drug, in a pH-dependent manner. The results indicate that the solvent-controlled self-assemblies may make the macromolecules good candidates for pH-controlled drug release carriers with good cell membrane permeability. This macromolecule may have potential applications in intracellular drug delivery systems.

Nanoscale Engineering and Optical Addressing of Single Spins in Diamond

The control of positioning of single atoms in solid becomes relevant for emerging technologies like spintronics and quantum information processing. [ 1–4 ] Quantum computing imposes strict requirements on the positioning of quantum bits (qubits). [ 5 ] The interaction between qubits needs to be stronger than the coupling to the environment in order to allow coherent quantum gates. Spins associated with defects in diamond are particularly promising candidates for solid state information carriers [ 6–8 ] owing to their long coherence time (seconds for nuclear spins and milliseconds for electron spin [ 9 ] ). Furthermore, when associated with color centres having spin-selective optical transitions (like the nitrogenvacancy (NV) centre), individual spins can be readout and polarized using optical techniques. Although spectacular experiments including two and three spins entanglement [ 10 ] or ultrafast control of spin qubits [ 11 ] were demonstrated recently, fully scalable architecture of diamond quantum registers requires the ability to create arrays of electron spins with a few nanometers accuracy. The NV centre in diamond consists of a vacancy and a nitrogen in the adjacent lattice position. It exists in two charge states: neutral and negatively charged. The energy structure

Dendrimers as carriers for contrast agents in magnetic resonance imaging

Magnetic resonance imaging (MRI) is a non-invasive clinical imaging modality, which has become widely used in the diagnosis of human diseases around the world. Some MRI exams include the use of contrast agents. The goal of an ideal MRI contrast agent involves the tissue- or organ-targeting materials with high relaxivity and specificity, low toxicity and side effects, suitable long intravascular duration and excretion time and high contrast enhancement with low doses, in vivo, all coupled to low overall cost. Dendrimers are synthetic, highly branched, mono-disperse macromolecules of nanometer dimensions. Properties associated with these dendrimers such as uniform size, water solubility, modifiable surface functionality and available internal cavities make them candidates for ideal carriers of MRI contrast agents. The research progress of the dendritic contrast agents is discussed.

ChemInform Abstract: The Synthesis of Highly Fluorinated Alkylcyclohexanes for Use as Oxygen Carriers and the 19F and 13C NMR Spectra of Alkylcyclohexanes.

Abstract Perfluoroalkylcyclohexanes are promising candidates for oxygen carriers. The perfluoroalkylcyclohexane analogues and 1H-perfluoroalkylcyclohexanes of n-propylcyclohexane, i-propylcyclohexane, n-butylcyclohexane, s-butylcyclohexane, i-butylcyclohexane and t-butylcyclohexane were prepared and characterized. Their properties and NMR spectra are discussed.

Synthesis and characterization of thermo-sensitive semi-IPN hydrogels based on poly(ethylene glycol)- co-poly(ε-caprolactone) macromer, N-isopropylacrylamide, and sodium alginate

Thermo-sensitive semi-IPN hydrogels were prepared via in situ copolymerization of N-isopropylacrylamide (NIPAAm) with poly(ethylene glycol)- co-poly(ε-caprolactone) (PEG- co-PCL) macromer in the presence of sodium alginate by UV irradiation technology. The effects of the sodium alginate content, temperature, and salt on the swelling behavior of the as-obtained hydrogels were studied. The results showed that the swelling ratio of the hydrogels increased with the increasing sodium alginate content at the same temperature, and decreased with the increase in temperature. The salt sensitivity of the semi-IPN hydrogels was dependent on the content of sodium alginate introduced in the hydrogels. The mechanical rheology of the hydrogels and in vitro release behavior of bovine serum albumin (BSA) in situ encapsulated within the hydrogels were also investigated. It was found that the introduction of sodium alginate with semi-IPN structure improved mechanical strength of the hydrogels and the cumulative release percentage of BSA from the hydrogels. Such double-sensitive semi-IPN hydrogel materials could be exploited as potential candidates for drug delivery carriers.

Bursting of sensitive polymersomes induced by curling

Polymersomes, which are stable and robust vesicles made of block copolymer amphiphiles, are good candidates for drug carriers or micro/nanoreactors. Polymer chemistry enables almost unlimited molecular design of responsive polymersomes whose degradation upon environmental changes has been used for the slow release of active species. Here, we propose a strategy to remotely trigger instantaneous polymersome bursting. We have designed asymmetric polymer vesicles, in which only one leaflet is composed of responsive polymers. In particular, this approach has been successfully achieved by using a UV-sensitive liquid-crystalline copolymer. We study experimentally and theoretically this bursting mechanism and show that it results from a spontaneous curvature of the membrane induced by the remote stimulus. The versatility of this mechanism should broaden the range of applications of polymersomes in fields such as drug delivery, cosmetics and material chemistry.

Hydrogen storage using heterocyclic compounds: The hydrogenation of 2-methylthiophene

Alkyl substituted thiophenes are promising candidates for hydrogen carriers, as their dehydrogenation reactions are known to occur under mild conditions. Four types of catalysts, including supported noble metals, bimetallic noble metals, transition metal phosphides and transition metal sulfides, have been investigated for 2-methylthiophene (2MT) hydrogenation and ring-opening. The major products were tetrahydro-2-methylthiophene (TH2MT), pentenes and pentane, with very little C 5-thiols observed. The selectivity towards the desired product TH2MT follows the order: noble metals > bimetallics > phosphides > sulfides. The best hydrogenation catalyst was 2% Pt/Al 2O 3 which exhibited relatively high reactivity and selectivity towards TH2MT at moderate temperatures. Temperature-programmed reaction (TPR) experiments revealed that pentanethiol became the major product, especially with HDS catalysts like CoMoS/Al 2O 3 and WP/SiO 2.

Biodegradable arginine-based poly(ester-amide)s as non-viral gene delivery reagents

A novel family of synthetic biodegradable poly(ester-amide)s (Arg-PEAs) was evaluated for their biosafety and capability to transfect rat vascular smooth muscle cells, a major cell type participating in vascular diseases. Arg-PEAs showed high binding capacity toward plasmid DNA, and the binding activity was inversely correlated to the number of methylene groups in the diol segment of Arg-PEAs. All Arg-PEAs transfected smooth muscle cells with an efficiency that was comparable to the commercial transfection reagent Superfect ®. However, unlike Superfect ®, Arg-PEAs, over a wide range of dosages, had minimal adverse effects on cell morphology, viability or apoptosis. Using rhodamine-labeled plasmid DNA, we demonstrated that Arg-PEAs were able to deliver DNA into nearly 100% of cells under optimal polymer-to-DNA weight ratios, and that such a high level of delivery was achieved through an active endocytosis mechanism. A large portion of DNA delivered, however, was trapped in acidic endocytotic compartments, and subsequently was not expressed. These results suggest that with further modification to enhance their endosome escape, Arg-PEAs can be attractive candidates for non-viral gene carriers owning to their high cellular uptake nature and reliable cellular biocompatibility.

Cellular Toxicity of Inorganic Hydroxide Nanoparticles

Layered double hydroxides (LDHs), anionic clays, have attracted increasing interest as nanovehicles for delivering genes, drugs, and bio-active molecules into cells. However, no attempts have been made to evaluate the potential undesirable effects of LDH nanoparticles. The cytotoxicity of LDHs with different chemical compositions (ZnAl- and MgAl-LDH) was systematically evaluated in various cell types, such as human normal cells, carcinoma cells, and red blood cells, by measuring cell viability, cell proliferation, membrane damage, and hemolytic effect. No significant cytotoxic effects could be seen in both cases, but ZnAl-LDH was determined to be slightly more toxic than MgAl-LDH in terms of membrane damage and hemolysis induction. It is, therefore, expected that LDHs could be promising candidates for novel inorganic drug delivery carriers.

Cellular Toxicity of Inorganic Hydroxide Nanoparticles

Layered double hydroxides (LDHs), anionic clays, have attracted increasing interest as nanovehicles for delivering genes, drugs, and bio-active molecules into cells. However, no attempts have been made to evaluate the potential undesirable effects of LDH nanoparticles. The cytotoxicity of LDHs with different chemical compositions (ZnAl- and MgAl-LDH) was systematically evaluated in various cell types, such as human normal cells, carcinoma cells, and red blood cells, by measuring cell viability, cell proliferation, membrane damage, and hemolytic effect. No significant cytotoxic effects could be seen in both cases, but ZnAl-LDH was determined to be slightly more toxic than MgAl-LDH in terms of membrane damage and hemolysis induction. It is, therefore, expected that LDHs could be promising candidates for novel inorganic drug delivery carriers.