Enhanced Antitumor Activity of the Photosensitizer meso-Tetra(N-methyl-4-pyridyl) Porphine Tetra Tosylate through Encapsulation in Antibody-Targeted Chitosan/Alginate Nanoparticles

meso-Tetra(N-methyl-4-pyridyl) porphine tetra tosylate (TMP) is a photosensitizer that can be used in photodynamic therapy (PDT) to induce cell death through generation of reactive oxygen species in targeted tumor cells. However, TMP is highly hydrophilic, and therefore, its ability to accumulate intracellularly is limited. In this study, a strategy to improve TMP uptake into cells has been investigated by encapsulating the compound in a hydrogel-based chitosan/alginate nanoparticle formulation. Nanoparticles of 560 nm in diameter entrapping 9.1 µg of TMP per mg of formulation were produced and examined in cell-based assays. These particles were endocytosed into human colorectal carcinoma HCT116 cells and elicited a more potent photocytotoxic effect than free drug. Antibodies targeting death receptor 5 (DR5), a cell surface apoptosis-inducing receptor up-regulated in various types of cancer and found on HCT116 cells, were then conjugated onto the particles. The conjugated antibodies further enhanced uptake and cytotoxic potency of the nanoparticle. Taken together, these results show that antibody-conjugated chitosan/alginate nanoparticles significantly enhanced the therapeutic effectiveness of entrapped TMP. This novel approach provides a strategy for providing targeted site-specific delivery of TMP and other photosensitizer drugs to treat colorectal tumors using PDT.

Facile synthesis of thiol-functionalized amphiphilic polylactide–methacrylic diblock copolymers

Biodegradable amphiphilic diblock copolymers based on an aliphatic ester block and various hydrophilic methacrylic monomers were synthesized using a novel hydroxyl-functionalized trithiocarbonate-based chain transfer agent. One protocol involved the one-pot simultaneous ring-opening polymerization (ROP) of the biodegradable monomer (3S)-cis-3,6-dimethyl-1,4-dioxane-2,5-dione (L-lactide, LA) and reversible addition–fragmentation chain transfer (RAFT) polymerization of 2-(dimethylamino)ethyl methacrylate (DMA) or oligo(ethylene glycol) methacrylate (OEGMA) monomer, with 4-dimethylaminopyridine being used as the ROP catalyst and 2,2′-azobis(isobutyronitrile) as the initiator for the RAFT polymerization. Alternatively, a two-step protocol involving the initial polymerization of LA followed by the polymerization of DMA, glycerol monomethacrylate or 2-(methacryloyloxy)ethyl phosphorylcholine using 4,4′-azobis(4-cyanovaleric acid) as a RAFT initiator was also explored. Using a solvent switch processing step, these amphiphilic diblock copolymers self-assemble in dilute aqueous solution. Their self-assembly provides various copolymer morphologies depending on the block compositions, as judged by transmission electron microscopy and dynamic light scattering. Two novel disulfide-functionalized PLA-branched block copolymers were also synthesized using simultaneous ROP of LA and RAFT copolymerization of OEGMA or DMA with a disulfide-based dimethacrylate. The disulfide bonds were reductively cleaved using tributyl phosphine to generate reactive thiol groups. Thiol–ene chemistry was utilized for further derivatization with thiol-based biologically important molecules and heavy metals for tissue engineering or bioimaging applications, respectively.

Artificial receptors for the extraction of nucleoside metabolite 7-methylguanosine from aqueous media made by molecular imprinting

A series of imprinted polymers targeting nucleoside metabolites, prepared using a template analogue approach, are presented. These were prepared following selection of the optimum functional monomer by solution association studies using 1H-NMR titrations whereby methacrylic acid was shown to be the strongest receptor with and affinity constant of 621 ± 51 L mol-1 vs. 110 ± 16 L mol-1 for acrylamide. The best performing polymers were prepared using methanol as porogenic co-solvent and although average binding site affinities were marginally reduced, 2.3×104 L mol-1 vs. 2.7×104 L mol-1 measured for a polymer prepared in acetonitrile, these polymers contained the highest number of binding sites, 5.27 μmol g-1¬¬ vs. 1.64 μmol g-1, while they also exhibited enhanced selectivity for methylated guanosine derivatives. When applied as sorbents in the extraction of nucleoside derivative cancer biomarkers from synthetic urine samples, significant sample clean-up and recoveries of up to 90% for 7-methylguanosine were achieved.

Generation of metallosupramolecular polymer gels from multiply functionalized grid-type complexes

A ditopic ligand (1), containing two tridentate bis(acylhydrazone) subunits and bearing both long alkyl chains and hydrogen-bonding groups, has been synthesised. Metal cation binding in the presence of a base leads to hierarchical self-assembly, forming first a neutral [2 x 2] grid-type complex (2) that hierarchically assembles into metallosupramolecular polymer gels in toluene.

Interactions of a non-thermal atmospheric pressure plasma effluent with PC-3 prostate cancer cells

The effect of a radio-frequency driven, microscale non thermal atmospheric pressure plasma jet operated in helium with vol. 0.3% molecular oxygen gas admixture, on PC-3 prostate cancer cells has been investigated. The viability of cells exposed to the plasma was found to decrease with increasing plasma exposure time, with apoptosis through caspase and PARP cleavage being observed. High concentrations of nitrite and nitrate were detected in growth media exposed to the plasma and were found to increase in a time dependent manner post exposure. This indicates a slow release of reactive nitrogen species into the growth media, which is likely to influence cellular response to plasma exposure.

Issues in fe modelling of FRP strengthened masonry arch bridges

Externally bonding of FRP composites is an effective technique for retrofitting historical masonry arch structures. A major failure mode in such strengthened structures is the debonding of FRP from the masonry. The bond behaviour between FRP and masonry thus plays a crucial role in these structures. Major challenges exist in the finite element modelling of such structures, such as modelling of mixed Mode-I and Mode-II bond behaviour between the FRP and the curved masonry substrate, modelling of existing damages in the masonry arches, consideration of loading history in the unstrengthened and strengthened structure etc. This paper presents a rigorous FE model for simulating FRP strengthened masonry arch structures. A detailed solid model was developed for simulating the masonry and a mixed-mode interface model was used for simulating the FRP-to-masonry bond behaviour. The model produces results in very close agreement with test results.

A technique for reducing strain concentrations in FRP wrapped concrete columns

Existing studies have shown conclusively that the measured fibre reinforced polymer (FRP) rupture strain in FRP wrapped concrete columns is usually significantly smaller than the rupture strain obtained from flat coupon tests. One of the main causes for this phenomenon is the existence of geometrical discontinuities at both ends of the FRP sheets. This study proposes a new strengthening method in which continuous FRP spiral wrapping is used to eliminate strain concentrations due to the geometrical discontinuities and thus increase the FRP rupture strain at column failure. The effect of the spiral angle of FRP on the FRP rupture strain in FRP wrapped specimens was experimentally investigated. The test results indicate that the spiral wrapping with a small angle with respect to the column circumference can significantly increase the strain efficiency of FRP and thus enhance the axial compression capacity of the strengthened cylinders.

FRP-to-concrete bond-slip behaviour under dynamic loading

Strengthening reinforced concrete (RC) structures by externally bonded FRP composites has been widely used for static loading and seismic retrofitting since 1990s. More recently many studies on strengthening concrete and masonry structures with externally bonded FRP for improved blast and impact resistance in protective engineering have also been conducted. The bond behaviour between the FRP and concrete plays a critical role in a strengthening system with externally bonded FRP. However, the understanding of how the bond between FRP and concrete performs under high strain rate is severely limited. Due to the dynamic characteristics of blast and impact loading, the bond behaviour between FRP and concrete under such loading is very different from that under static loading. This paper presents a study on the dynamic bond-slip behaviour based on both the numerical analysis and test results. A dynamic bond-slip model is proposed in this paper.

Bond behavior of NSM FRP strips between two adjacent cracks in concrete beams: A numerical study

Strengthening RC structures with near-surface mounted (NSM) fibre reinforced polymer (FRP) composites has a number of advantages compared with that with externally bonded (EB) FRP sheets/plates. As with EB FRP, the performance of the bond between NSM FRP and concrete is one of the key factors affecting the behaviour of the strengthened structure. This paper presents a numerical investigation into the behaviour of NSM FRP loaded at its both ends to simulate the NSM FRP-toconcrete bond between two adjacent cracks in RC members. The main objective of this study is to quantitatively clarify the effect of the bondline damage during slip reversal on the ultimate load (bond strength). The results show that the bondline damage has a significant effect on the load-carrying capacity of the NSM FRP-to-concrete bonded interface and should be considered in FE modeling of the interface.

Interpretation of flat FRP coupon test results

The tensile strength obtained from existing testing methods such as ASTM D3039, based on flat coupons, usually has a large scatter for fibre reinforced polymer (FRP) composites. This means that the measured strength may not represent the actual strength of the material, leading to under or over design. This paper develops a new interpretation method which requires fewer tests, saving money and time. Moreover the results are more consistent and more closely represent the actual strength which can lead to a safer and more economical design.

Mitigation of concrete cover separation in frpstrengthened RC beams using FRP U-jackets

Concrete cover separation is a common failure mode of reinforced concrete (RC) beams strengthened with a fibre-reinforced polymer (FRP) plate bonded to the tension face (FRP-plated RC beams). Plate-end FRP U-jackets have previously been explored as a mitigation measure to delay or suppress concrete cover separation, although its effectiveness needs further clarification. The paper presents the first systemic experimental study on the use of FRP U-jackets of different forms for mitigating the concrete cover separation failure. A total of ten full-scale FRP-plated RC beams were tested. The test results show that both the ultimate load and the ductility of the beams were enhanced by the U-jackets. Among the forms of U-jackets explored, those inclined at 45o are the most effective.

Strengthening timber beams with near surface mounted carbon fiber reinforced polymer rods

Many timber structures may require strengthening due to either decay and aging or an increase of load. This paper presents an experimental study in which eleven timber beams were tested, including three unstrengthened reference beams and eight beams strengthened with NSM CFRP bars. The test parameters include the position of NSM (tensile face or the bottom of the sides), the number of CFRP bars (1 or 2), and additional anchorage of NSM CFRP bars (steel wire U anchors or CFRP U strips). The test results show that the ultimate flexural strength of the timber beams were increased by 14%∼85% with an average of 47% due to NSM CFRP bar strengthening. Their deflection corresponding to the peak load was increased by 33% in average.

Improved shear strength model for FRP-strengthened RC beams accounting for adverse FRP-steel interaction

RC beams shear-strengthened with externally-bonded FRP side strips or U-strips usually fail by debonding. As such debonding occurs in a brittle manner at relatively small shear crack widths, some of the internal steel stirrups may not have reached yielding at beam shear failure. Consequently, the internal steel stirrups cannot be fully utilized. This adverse shear interaction between internal steel stirrups and external FRP strips may significantly reduce the benefit of shear-strengthening FRP but has not been considered by any of the existing FRP strengthening design guidelines. In this paper, an improved shear strength model capable of accounting for the effect of the above shear interaction is first presented, in which the unfavorable effect of shear interaction is reflected through a reduction factor (i.e. shear interaction factor). Using a large test database established in the present study, the performance of the proposed model as well as that of three other shear strength models is then assessed. This assessment shows that the proposed shear strength model performs better than the three existing models. The assessment also shows that the inclusion of the proposed shear interaction factor in the existing models can significantly improve their performance.

Effects of unconfined concrete strength on FRP confinement of concrete

Research has shown that fibre reinforced polymer (FRP) wraps are effective for strengthening concrete columns for increased axial and flexural load and deformation capacity, and this technique is now used around the world. The experimental study presented in this paper is focused on the mechanics of FRP confined concrete, with a particular emphasis on the influence of the unconfined concrete compressive strength on confinement effectiveness and hoop strain efficiency. An experimental programme was undertaken to study the compressive strength and stress-strain behaviour of unconfined and FRP confined concrete cylinders of different concrete strength but otherwise similar mix designs, aggregates, and constituents. This was accomplished by varying only the water-to-cement ratio during concrete mixing operations. Through the use of high-resolution digital image correlation to measure both axial and hoop strains, the observations yield insights into the mechanics of FRP confinement of concretes of similar composition but with varying unconfined concrete compressive strength.

Novel manually made NSM FRP (MMFRP) bars for shear strengthening of RC beams

This paper presents an experimental study evaluating the effectiveness of the Near Surface Mounted (NSM) technique with innovative manually made FRP bars (MMFRP) for shear strengthening of RC beams. RC beams designed to fail in shear were tested in three-point bending. To delay the onset of MMFRP bar debonding, a new anchorage is also developed and tested. This paper reports the results of a series of tests on simply supported rectangular RC beams, strengthened in shear with MMFRP bar either with or without the proposed anchorage. The load-deflection responses of all test beams are plotted, in addition to selected strain results. Performance and the failure modes of the test beams are presented and discussed in this paper. The proposed MMFRP bars and end anchorage enhanced the shear capacity between 25 to 48% over the control specimen. Furthermore, the adoption of the proposed end anchorage of MMFRP bars significantly enhanced the ductility of the test specimens.