Accurate measurement and enhancement of fiber coil symmetry.

The pure Shupe effect is substantially reduced in a fiber optic gyroscope (FOG) with symmetrical windings. However, the effect of the temperature-induced nonuniformity of the stress in the coil depends on the mean temperature derivative (T-dot). Research on precision winding technology has discovered that the symmetry of optical fiber rings affects the temperature performance of fiber optic gyroscopes. Optical fiber rings with good symmetry also have good temperature performance. This paper first establishes a temperature drift model of optical fiber rings that includes the Shupe effect and T-dot effect and then uses finite element simulation to analyze the drift error of optical fiber rings in a variable temperature environment. Analysis shows that this drift is caused by the variation and uneven distribution of the fiber length and the refractive index in the positive and negative winding of the optical fiber ring, which results in a residual phase difference that is directly related to the symmetry of the optical fiber ring. Simulation and analysis show that balancing the residual phase difference of the optical fiber ring can be achieved by cutting the length of the optical fiber ring at both ends. This paper uses optical frequency domain reflectometry (OFDR) technology to precisely test the symmetry of the optical fiber ring, ensuring accurate adjustment of the lengths at both ends of the optical fiber ring. Experimental tests on two gyroscopes have shown that the optical fiber ring with a smaller drift error can be obtained after testing and adjusting its length. The experimental data indicates that the bias stability of two laboratory gyros are increased by 23.6% and 18.1%, and the bias range are reduced by 22.4% and 30.0%.

Precisely Shaped Self-Adjuvanting Peptide Vaccines with Enhanced Immune Responses for HPV-Associated Cancer Therapy.

Peptide vaccines exhibit great potential in cancer therapy via eliciting antigen-specific host immune response and long-term immune memory to defend cancer cells. However, the low induced immune response of many developing vaccines implies the imperatives for understanding the favorable structural features of efficient cancer vaccines. Herein, we report on the two groups of self-adjuvanting peptide vaccines with distinct morphology and investigate the relationship between the morphology of peptide vaccines and the induced immune response. Two nanofibril peptide vaccines were created via co-assembly of a pentapeptide with a central 4-aminoproline residue, with its derivative functionalized with antigen epitopes derived from human papillomavirus E7 proteins, whereas utilization of a pentapeptide with a natural proline residue led to the formation of two nanoparticle peptide vaccines. The immunological results of dendritic cell (DCs) maturation and antigen presentation induced by the peptide assemblies implied the self-adjuvanting property of the resulting peptide vaccines. In particular, cellular uptake studies revealed the enhanced internalization and elongated retention of the nanofibril peptide vaccines in DCs, leading to their advanced performance in DC maturation, accumulation at lymph nodes, infiltration of cytotoxic T lymphocytes into tumor tissues, and eventually lysis of in vivo tumor cells, compared to the nanoparticle counterparts. The antitumor immune response caused by the nanofibril peptide vaccines was further augmented when simultaneously administrated with anti-PD-1 checkpoint blockades, suggesting the opportunity of the combinatorial immunotherapy by utilizing the nanofibril peptide vaccines. Our findings strongly demonstrate a robust relationship between the immune response of peptide vaccines and their morphology, thereby elucidating the critical role of morphological control in the design of efficient peptide vaccines and providing the guidance for the design of efficient peptide vaccines in the future.

Self-assembly of virulent amyloid-derived peptides into nanoantibacterials.

Current strategies for the design of antibacterial peptides show limitations in the development of assembled antibacterial peptides due to the challenges in simultaneously balancing the antibacterial activity and assembling behavior. Herein, we report on one strategy for the design of antibacterial peptides derived from virulent amyloids and investigate their self-assembly into nanostructures with remarkable antibacterial activity. The peptides were either directly truncated from virulent amyloid peptide PSM α3 or mutated from the original sequence by replacing the lysine and phenylalanine residues with arginine or tryptophan, leading to three undecapeptides. Conformational and morphological results indicated the formation of nanotubes and twisted nanoribbons by the truncated peptide and the mutated peptide, respectively, predominately driven by anti-parallel ß-sheets. Bacterial culturing experiments revealed that the two mutated peptides possessed remarkable antibacterial activity against both Gram-positive and Gram-negative bacteria by disrupting the bacterial membrane at a concentration above their critical aggregation concentrations, thus leading to two nanoantibacterials. Our findings demonstrate that biomimetic peptides originated from virulent amyloids exhibit great potential in the development of assembled antibacterial peptides, thus providing a new strategy for simultaneously addressing the antibacterial activity and pharmacokinetics of natural antibacterial peptides in the future.

Peptide Tectonics: Encoded Structural Complementarity Dictates Programmable Self-Assembly.

Programmable self-assembly of peptides into well-defined nanostructures represents one promising approach for bioinspired and biomimetic synthesis of artificial complex systems and functional materials. Despite the progress made over the past two decades in the development of strategies for precise manipulation of the self-assembly of peptides, there is a remarkable gap between current peptide assemblies and biological systems in terms of structural complexity and functions. Here, the concept of peptide tectonics for the creation of well-defined nanostructures predominately driven by the complementary association at the interacting interfaces of tectons is introduced. Peptide tectons are defined as peptide building blocks exhibiting structural complementarity at the interacting interfaces of commensurate domains and undergoing programmable self-assembly into defined supramolecular structures promoted by complementary interactions. Peptide tectons are categorized based on their conformational entropy and the underlying mechanism for the programmable self-assembly of peptide tectons is highlighted focusing on the approaches for incorporating the structural complementarity within tectons. Peptide tectonics not only provides an alternative perspective to understand the self-assembly of peptides, but also allows for precise manipulation of peptide interactions, thus leading to artificial systems with advanced complexity and functions and paves the way toward peptide-related functional materials resembling natural systems.

Pancreatic islet surface engineering with a starPEG-chondroitin sulfate nanocoating.

Islet transplantation is one of the most promising therapeutic options that could restore euglycaemia in type 1 diabetic individuals. The currently implemented alginate microsphere islet encapsulation approach has led to positive outcomes in improving intraportal islet delivery in rodents. However, results obtained from human clinical trials remain disappointing. The less than satisfactory clinical outcome is mainly attributable to the increased size of the encapsulated islet and alginate-elicited host immune responses. In order to achieve islet encapsulation without significant alteration of the islet size, we designed and prepared a chondroitin sulfate (CS)-incorporated starPEG nanocoating (CS-PEG) that conjugates covalently to the pancreatic islet cell surface amine groups via pseudo-orthogonal chemistry for islet surface engineering. CS-PEG surface engineering incurred minimal alteration of the islet volume. Enhanced in situ revascularization, which is protective against extracellular matrix disruption, was also observed from CS-PEG islets in addition to robust islet viability and uncompromised insulin secretory ability. More importantly, CS-PEG surface engineering reduced blood coagulation while facilitating islet cell survival under pro-inflammatory conditions. Given that host immune rejection and an instant blood-mediated inflammatory reaction (IBMIR) are the primary factors detrimental to islet engraftment and survival, often resulting in rapid cell loss and graft failure, CS-PEG surface engineering provides an "easy-to-adopt" approach for cell surface engineering that could potentially improve the clinical efficacy of islet transplantation and other types of cell therapies.

Polar-π Interactions Promote Self-assembly of Dipeptides into Laminated Nanofibers.

Precise incorporation of functional residues into sequences allows for tailoring the noncovalent interactions between peptides to guide their self-assembly into well-defined nanostructures, thus facilitating creation of artificial functional materials resembling natural systems. Here, we report on the self-assembly of dipeptides consisting of one fluorinated phenylalanine unit (Z residue) and one natural aromatic residue into laminated nanofibers predominately driven by polar-π interactions. On the basis of characterizations using transmission electron microscopy, scanning electron microscopy, atomic force microscopy, circular dichroism, Fourier transform infrared spectroscopy, and thioflavin T binding assay, we found that the face-centered stacking pattern of the dipeptides FZ, ZF, and ZY stabilized by the polar-π interactions and antiparallel ß-sheet H-bonding interactions led to lamination of nanofibers and formation of ribbonlike nanostructures. Our findings demonstrate that incorporation of fluorinated aromatic units into short peptides not only promotes of polar-π interactions as alternative self-assembling driving forces but also governs the organizing pattern of peptides, thus benefiting creation of well-defined peptide nanostructures.

Surface Engineering of Pancreatic Islets with a Heparinized StarPEG Nanocoating.

Cell surface engineering can protect implanted cells from host immune attack. It can also reshape cellular landscape to improve graft function and survival post-transplantation. This protocol aims to achieve surface engineering of pancreatic islets using an ultrathin heparin-incorporated starPEG (Hep-PEG) nanocoating. To generate the Hep-PEG nanocoating for pancreatic islet surface engineering, heparin succinimidyl succinate (Heparin-NHS) was first synthesized by modification of its carboxylate groups using N-(3-dimethylamino propyl)-N'-ethyl carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). The Hep-PEG mixture was then formed by crosslinking of the amino end-functionalized eight-armed starPEG (starPEG-(NH2)8) and Heparin-NHS. For islet surface coating, mouse islets were isolated via collagenase digestion and gradient purification using Histopaque. Isolated islets were then treated with ice cold Hep-PEG solution for 10 min to allow covalent binding between NHS and the amine groups of islet cell membrane. Nanocoating with the Hep-PEG incurs minimal alteration to islet size and volume and heparinization of the islets with Hep-PEG may also reduce instant blood-mediated inflammatory reaction during islet transplantation. This "easy-to-adopt" approach is mild enough for surface engineering of living cells without compromising cell viability. Considering that heparin has shown binding affinity to multiple cytokines, the Hep-PEG nanocoating also provides an open platform that enables incorporation of unlimited functional biological mediators and multi-layered surfaces for living cell surface bioengineering.

Pancreatic islet surface bioengineering with a heparin-incorporated starPEG nanofilm.

Cell surface engineering could protect implanted cells from host immune rejections while modify the cellular landscape for better post-transplantation graft function and survival. Islet transplantation is considered the most promising therapeutic option with the potential to cure diabetes. Current approach to improve clinical efficacy of pancreatic islet transplantation is alginate encapsulation. However, disappointing outcomes have been reported in clinical trials due to larger islet size resulted by encapsulation and alginate-elicited host immune responses. We have developed an ultrathin nanofilm of starPEG with incorporated heparin (Hep-PEG) that binds covalently to the amine groups of islet surface membrane via its N-hydroxysuccinimide groups. The Hep-PEG nanocoating elicited minimal alteration on islet volume in culture. Hep-PEG-coated islets exhibited robust islet viability accompanied by uncompromised islet insulin secretory function. Instant blood-mediated inflammatory reaction was also reduced by Hep-PEG islet coating, accompanied by enhanced intra-islet revascularization. In addition, despite its semi-permeability, Hep-PEG islet coating promoted the survival of islets exposed to pro-inflammatory cytokines. Considering that inflammation and hypoxia are primary causes of immediate cell loss for cell therapy, the Hep-PEG nanofilm represents a viable approach for cell surface engineering which would improve the clinical outcome of cell therapies.

Preparation of a dual cored hepatoma-specific star glycopolymer nanogel via arm-first ATRP approach.

A reductase-cleavable and thermo-responsive star-shaped polymer nanogel was prepared via an "arm-first" atom transfer radical polymerization approach. The nanogel consists of a thermo- and redox-sensitive core and a zwitterionic copolymer block. The dual sensitive core is composed of poly(N-isopropylacrylamide) that is formed by disulfide crosslinking of N-isopropylacrylamide. The zwitterionic copolymer block contains a poly(sulfobetaine methacrylate) component, a known anti-adsorptive moiety that extends blood circulation time, and a lactose motif of poly(2-lactobionamidoethyl methacrylamide) that specifically targets the asialoglycoprotein receptors (ASGP-Rs) of hepatoma. Doxorubicin (DOX) was encapsulated into the cross-linked nanogels via solvent extraction/evaporation method and dialysis; average diameter of both blank and DOX-loaded nanogels was ~120 nm. The multi-responsiveness of nanogel drug release in different temperatures and redox conditions was assessed. After 24 h, DOX release was only ~20% at 30°C with 0 mM glutathione (GSH), whereas over 90% DOX release was observed at 40°C and 10 mM GSH, evidence of dual responsiveness to temperature and reductase GSH. The IC50 value of DOX-loaded nanogels was much lower in human hepatoma (HepG2) cells compared to non-hepatic HeLa cells. Remarkably, DOX uptake of HepG2 cells differed substantially in the presence and absence of galactose (0.31 vs 1.42 µg/mL after 48 h of incubation). The difference was non-detectable in HeLa cells (1.21 vs 1.57 µg/mL after 48 h of incubation), indicating that the overexpression of ASGP-Rs leads to the DOX-loaded lactosylated nanogels actively targeting hepatoma. Our data indicate that the lactose-decorated star-shaped nanogels are dual responsive and hepatoma targeted, and could be employed as hepatoma-specific anti-cancer drug delivery vehicle for cancer chemotherapy.

Galactose-functionalized multi-responsive nanogels for hepatoma-targeted drug delivery.

We report here a hepatoma-targeting multi-responsive biodegradable crosslinked nanogel, poly(6-O-vinyladipoyl-D-galactose-ss-N-vinylcaprolactam-ss-methacrylic acid) P(ODGal-VCL-MAA), using a combination of enzymatic transesterification and emulsion copolymerization for intracellular drug delivery. The nanogel exhibited redox, pH and temperature-responsive properties, which can be adjusted by varying the monomer feeding ratio. Furthermore, the volume phase transition temperature (VPTT) of the nanogels was close to body temperature and can result in rapid thermal gelation at 37 °C. Scanning electron microscopy also revealed that the P(ODGal-VCL-MAA) nanogel showed uniform spherical monodispersion. With pyrene as a probe, the fluorescence excitation spectra demonstrated nanogel degradation in response to glutathione (GSH). X-ray diffraction (XRD) showed an amorphous property of DOX within the nanogel, which was used in this study as a model anti-cancer drug. Drug-releasing characteristics of the nanogel were examined in vitro. The results showed multi-responsiveness of DOX release by the variation of environmental pH values, temperature or the availability of GSH, a biological reductase. An in vitro cytotoxicity assay showed a higher anti-tumor activity of the galactose-functionalized DOX-loaded nanogels against human hepatoma HepG2 cells, which was, at least in part, due to specific binding between the galactose segments and the asialoglycoprotein receptors (ASGP-Rs) in hepatic cells. Confocal laser scanning microscopy (CLSM) and flow cytometric profiles further confirmed elevated cellular uptake of DOX by the galactose-functionalised nanogels. Thus, we report here a multi-responsive P(ODGal-VCL-MAA) nanogel with a hepatoma-specific targeting ability for anti-cancer drug delivery.

Galactose functionalized injectable thermoresponsive microgels for sustained protein release.

Novel galactose functionalized thermoresponsive injectable microgels, poly(N-isopropylacrylamide-co-6-O-vinyladipoyl-D-galactose) P(NIPAAm-co-VAGA), have been fabricated using a combination of enzymatic transesterification and emulsion copolymerization. The microgels exhibit reversible temperature-responsive behavior, which can be tuned by varying the monomer feed ratio. The lower critical solution temperatures (LCSTs) of the materials are close to body temperature and can result in a rapid thermal gelation at 37 °C. Field emission scanning electron microscopy showed the resultant microgels to have porous structures, and dynamic light scattering experiments indicated a dramatic reduction in particle size as solutions of the polymers are heated through the LCST. The polymers can be loaded with protein (bovine serum albumin; BSA), and in vitro studies showed that the BSA release kinetics depend upon the temperature and copolymer composition. Microgels based on P(NIPAAm-co-VAGA) could hence serve as candidates for site-specific sustained release drug delivery systems.

Fabrication and aggregation of thermoresponsive glucose-functionalized double hydrophilic copolymers.

Novel double-hydrophilic thermosensitive statistical glycopolymers, poly(N-isopropylacrylamide-co-6-O-vinyladipoyl-D-glucose), were fabricated using a chemoenzymatic process and free radical copolymerization. The structures of the glycopolymers were confirmed by (1)H and (13)C NMR, and their molar mass distributions determined by gel permeation chromatography. UV-vis spectroscopy data showed that the polymers exhibited reproducible temperature-responsive behavior. The self-assembly and critical aggregation concentration was verified by fluorescence spectroscopy with pyrene acting as a hydrophobic probe. Measurements by laser light scattering and transmission electron microscopy revealed that the glycopolymers were able to self-assemble into aggregates with varying particle sizes and morphologies in aqueous solutions.

A systematic study of captopril-loaded polyester fiber mats prepared by electrospinning.

In this study, drug-loaded nanofibers were prepared by electrospinning captopril (CPL) with aliphatic biodegradable polyesters. Poly(L-lactic acid) (PLLA), poly(lactic-co-glycolic acid) (PLGA), and poly(lactic-co-ε-caprolactone) (PLCL) were used as filament-forming matrix polymers, and the concentration of CPL in each fiber type was varied. Scanning electron microscopy indicated that the morphology and diameters of the fibers were influenced by the concentration of polymer in the spinning solution and the drug loading. CPL was found to be distributed in the polymer fibers in an amorphous manner using differential scanning calorimetry and X-ray diffraction. FTIR indicated that hydrogen bonding existed between the drug molecules and the carrier polymers. In vitro dissolution tests showed that drug release from the fibers was highly dependent on the release medium, temperature, and on the polymer used. A range of kinetic models were fitted to the drug-release data obtained, and indicated that release was diffusion controlled in all cases. The different polymer fibers have application in diverse areas of drug delivery, for instance as sub-lingual or sustained release systems. Furthermore, by combining different CPL-loaded fibers, it would be possible to produce a bespoke formulation with tailored drug-release properties.