Mannose Molecules Research Articles

Cyclodextrin-based supramolecular nanogels decorated with mannose for short peptide encapsulation

Nanogels are aqueous dispersions of hydrogel particles formed by physically or chemically cross-linked polymer networks of nanoscale size. Herein, we devised a straightforward technique to fabricate a novel class of physically cross-linked nanogels via a self-assembly process in water involving α-cyclodextrin and a mannose molecule that was hydrophobically modified using an alkyl chain. The alkyl chain-modified mannose was synthesized in five steps, starting with D-mannose. Subsequently, nanogels were formed by subjecting α-cyclodextrin and the hydrophobically modified mannose to magnetic stirring in water. By adjusting the mole ratio between the hydrophobically modified mannose and α-cyclodextrin, nanogels with an average 100–150 nm diameter were obtained. Physicochemical and structural analyses by 1H NMR and X-ray diffraction unveiled a supramolecular and hierarchical mechanism underlying the creation of these nanogels. The proposed mechanism of nanogel formation involves two distinct steps: initial interaction of hydrophobically modified mannose with α-cyclodextrin resulting in the formation of inclusion complexes, followed by supramolecular interactions among these complexes, ultimately leading to nanogel formation after 72 h of stirring. We demonstrated the nanogels’ ability to encapsulate a short peptide ([p-tBuF2, R5]SHf) as a water-soluble drug model. This discovery holds promise for potentially utilizing these nanogels in drug delivery applications.

Carbohydrate-binding ability of a recombinant protein containing the DM9 motif from Drosophila melanogaster.

Proteins containing DM9 motifs, which were originally identified in the Drosophila melanogaster genome, are widely distributed in various organisms and are assumed to be involved in their innate immune response. In this study, we produced a recombinant protein of CG13321 (rCG13321) from D. melanogaster, which consists of four DM9 motifs, in Escherichia coli cells. In affinity chromatography using a mannose-immobilized column, rCG13321 exhibited mannose-binding ability and was separated into high-affinity and low-affinity fractions, named HA and LA, respectively, based on its binding ability to the column. In addition to having a higher affinity for the column, HA exhibited self-oligomerization ability, suggesting slight differences in tertiary structure. Both LA and HA showed hemagglutinating activity and were able to agglutinate an oligomannose-containing dendrimer, indicating that they have multiple carbohydrate-binding sites. Glycan array analysis suggested that rCG13321 primarily recognizes D-mannose and D-rhamnose through hydrogen bonding with the 2-, 3-, and 4-hydroxy groups. Isothermal titration calorimetry demonstrated that rCG13321 has a comparable affinity to typical lectins. These findings suggest that CG13321 functions as a carbohydrate-binding protein or lectin that recognizes mannose and related carbohydrate-containing molecules on the surface of foreign organisms as a pattern recognition molecule.

An atomistic scale simulation study of structural properties in the silk-fibrohexamerin complex.

The use of Bombyx mori silk fibroin in composite materials has been extensively explored in many studies, owing to its remarkable mechanical properties. Recently, the N-glycan-engineered P25 protein was utilized to improve the mechanical properties of silk. However, the mechanism by which N-glycan-engineered P25 protein enhances the mechanical properties of silk remains unclear. This study analyzed the interaction between the P25 protein and silkworm silk using quantum mechanics/molecular mechanics multiscale simulations and discovered stronger hydrogen bonding between the amorphous domain and the P25 protein. The results confirmed that glycoengineering of the mannose molecule in N-glycan in orders of three, five, and seven increased the hydrogen bonding of the amorphous structures. However, P25 has fewer binding interactions with the crystalline domain. Silk amino acids and mannose molecules were analyzed using QM simulations, and hydroxyl and charged amino acids in the amorphous domains were found to have relatively higher reactivity with mannose molecules in N-glycans than basic and aliphatic amino acids in the crystalline domain. This study demonstrates how the N-glycan-engineered P25 protein can improve the mechanical properties of silk fibroin and identifies a key factor for N-glycan-engineered proteins.

A Polarity-Sensitive Far-Red Fluorescent Probe for Glucose Sensing through Skin.

The field of glucose biosensors for diabetes management has been of great interest over the past 60 years. Continuous glucose monitoring (CGM) is important to continuously track the glucose level to provide better management of the disease. Concanavalin A (ConA) can reversibly bind to glucose and mannose molecules and form a glucose biosensor via competitive binding. Here, we developed a glucose biosensor using ConA and a fluorescent probe, which generated a fluorescent intensity change based on solvatochromism, the reversible change in the emission spectrum dependent on the polarity of the solvent. The direction in which the wavelength shifts as the solvent polarity increases can be defined as positive (red-shift), negative (blue-shift), or a combination of the two, referred to as reverse. To translate this biosensor to a subcutaneously implanted format, Cyanine 5.5 (Cy5.5)-labeled small mannose molecules were used, which allows for the far-red excitation wavelength range to increase the skin penetration depth of the light source and returned emission. Three Cy5.5-labeled small mannose molecules were synthesized and compared when used as the competing ligand in the competitive binding biosensor. We explored the polarity-sensitive nature of the competing ligands and examined the biosensor's glucose response. Cy5.5-mannotetraose performed best as a biosensor, allowing for the detection of glucose from 25 to 400 mg/dL. Thus, this assay is responsive to glucose within the physiologic range when its concentration is increased to levels needed for an implantable design. The biosensor response is not statistically different when placed under different skin pigmentations when comparing the percent increase in fluorescence intensity. This shows the ability of the biosensor to produce a repeatable signal across the physiologic range for subcutaneous glucose monitoring under various skin tones.

Glycolysis inhibition for synergistic phototherapy of triple-negative breast cancer.

Phototherapy is a local and precise therapeutic technique for tumor treatment. However, the therapeutic effects of photothermal and photodynamic therapies are inevitably encountered by hypoxia of the tumor microenvironment and heat shock protein induced by hyperthermia, respectively. Herein, we found that mannose, a glucose analog, could reverse tumor hypoxia by inhibiting glycolysis of cancer cells and suppressing the expression of heat shock protein through inhibiting cellular adenosine triphosphate (ATP) generation. Next, we used lipid nanoparticles simultaneously loaded with indocyanine green (ICG) and mannose molecules, named imLipo, for tumor therapy. Both in vitro and in vivo experiments evidenced that the imLipo nanoplatform has significant therapeutic efficacy through synergistic phototherapy under single near-infrared laser irradiation. This work shows that glycolysis inhibition can overcome the challenges of phototherapy. In addition, all three parts (mannose, ICG, and lipid) of imLipo are clinically approved and our designed nanoplatforms have great potential for future tumor treatment.

Circulation Time-Optimized Albumin Nanoplatform for Quantitative Visualization of Lung Metastasis via Targeting of Macrophages.

The development of molecular imaging probes to identify key cellular changes within lung metastases may lead to noninvasive detection of metastatic lesions in the lung. In this study, we constructed a macrophage-targeted clickable albumin nanoplatform (CAN) decorated with mannose as the targeting ligand using a click reaction to maintain the intrinsic properties of albumin in vivo. We also modified the number of mannose molecules on the CAN and found that mannosylated serum albumin (MSA) harboring six molecules of mannose displayed favorable pharmacokinetics that allowed high-contrast imaging of the lung, rendering it suitable for in vivo visualization of lung metastases. Due to the optimized control of functionalization and surface modification, MSA enhanced blood circulation time and active/passive targeting abilities and was specifically incorporated by mannose receptor (CD206)-expressing macrophages in the metastatic lung. Moreover, extensive in vivo imaging studies using single-photon emission computed tomography (SPECT)/CT and positron emission tomography (PET) revealed that blood circulation of time-optimized MSA can be used to discern metastatic lesions, with a strong correlation between its signal and metastatic burden in the lung.

Pharmacological and Phytochemical Potential of Aleo Barbadensis (A Comprehensive Review)

Aloe vera contains 99-99.5% water; the remaining (0.5- 1.0%) solid material is comprised of minerals, water & fat-soluble vitamins, amino acids, phenolic compounds, simple and complex polysaccharides and organic acids. Aloe gel contains different elements like B, Be, Al, P, Si, Ca, Mg, Na and Fe. On the basis of dry-weight, the rind and pulp contain only a minor fraction of proteins and lipids. Gel polysaccharides of Aloe vera are comprised of linear chains of glucose and mannose molecules. Aloe vera consists of more than 200 different biological and medicinal active ingredients which are highly beneficial for human health. The plant demonstrates the antibacterial and antifungal, anti-helmenthic, purgative, anti-inflammatory, aphrodisiac, antispectic, anti-oxiant and laxative properties and is also used to treat skin infections, skin cancer, minor cuts and even sunburns; it is also effective against piles, jaundice, cough, dyspnea and asthma. The plant is commonly used at local level in Pakistan, for the treatment of numerous human diseases. Aloe vera also finds very important applications in cosmetics, dermatological industry, beauty products, sun block lotions, skin smoothening moisturizers, skin tonics against pimples and also have the ability to transport healthy substances through the skin and removal of dead skin cells. The present study was aimed to review the phytochemical composition and medicinal potential of Aloe barbadensis (Aloe vera) which is a very famous plant all over the world.

Surface Functionalization of Polymer Particles for Cell Targeting by Modifying Emulsifier Chemistry.

The oil in water emulsion/solvent extraction method is used to fabricate many FDA approved, polymer particle formulations for drug delivery. However, these formulations do not benefit from surface functionalization that can be achieved through tuning particle surface chemistry. Poly(vinyl alcohol) (PVA) is the emulsifier used for many FDA approved formulations and remains associated with the particle surface after fabrication. We hypothesized that the hydroxyl groups in PVA could be conjugated with biomolecules using isothiocyanate chemistry and that these modifications would endow the particle surface with additional functionality. We demonstrate that fluorescein isothiocyanate and an isothiocyanate derivatized mannose molecule can be covalently attached to PVA in a one-step reaction. The modified PVA polymers perform as well as unmodified PVA in acting as an emulsifier for fabrication of poly(lactide-co-glycolide) particles. Particles made with the fluorescein modified PVA exhibit fluorescence confined to the particle surface, while particles made with mannose modified PVA bind concanavalin A. In addition, mannose modified PVA increases particle association with primary macrophages by three-fold. Taken together, we present a facile method for modifying the surface reactivity of polymer particles widely used for drug delivery in basic research and clinical practice. Given that methods are established for conjugating the isothiocyanate functional group to a wide range of biomolecules, our approach may enable PVA based biomaterials to engage a multitude of biological systems.

Techno-functional properties and immunomodulatory potential of exopolysaccharide from Lactiplantibacillus plantarum MM89 isolated from human breast milk

An exopolysaccharide, designated as MM89-EPS, was isolated from Lactiplantibacillus plantarum MM89. It was comprised of glucose and mannose molecules with an average molecular weight of 138 kDa. FTIR and NMR spectra showed that MM89-EPS had characteristic polysaccharide functional groups. MM89-EPS displayed excellent water solubility and capacities to retain water and oil due to its porous structure. MM89-EPS exhibited no significant cytotoxicity on RAW264.7 cells and showed strong immunomodulatory activity by increasing phagocytosis, acid phosphatase activity, and cytokine production in RAW264.7 cells. Furthermore, an in vivo study revealed that splenic indices, intestinal IgA levels, serum cytokine levels, and lymphocyte proliferation were increased in an MM89-EPS-treated cyclophosphamide-induced immunosuppressed mouse model. To summarize, our results indicate that MM89-EPS can efficiently enhance the immunostimulatory activity of immune cells and an immunosuppressed mouse model. Hence, MM89-EPS may be use as a potential source of immunomodulatory agent in various food products.

Reversing tumor immunosuppressive microenvironment via targeting codelivery of CpG ODNs/PD-L1 peptide antagonists to enhance the immune checkpoint blockade-based anti-tumor effect

In order to reverse tumor immunosuppressive microenvironment and improve antitumor immune effect based on immune checkpoint blocking, a mannose-modified liposome-based CpG ODNs and PD-L1 antagonistic peptides (P) co-delivery system (HA/M-Lipo CpG-P) was constructed, in which hyaluronic acid (HA) coating was supposed to improve the systemic circulation stability and thereby promote its accumulation in tumor tissues. When the HA/M-Lipo CpG-P complexes enter the tumor tissues, HA will be hydrolyzed under the action of hyaluronidase, exposing P peptides. Then, P peptides linked by octapeptides that can be cleaved by matrix metalloproteinases (MMPs) are released into tumor tissues under the action of MMPs, exerting a blocking effect in the PD-1/PD-L1 pathway. The M-Lipo CpG complexes can recognize macrophage surface mannose receptors through its surface modified mannose molecules, and promote the intracellular delivery of CpG ODNs, thereby activating macrophages. The results showed that HA/M-Lipo CpG-P complexes successfully reversed M2-type macrophages in tumor microenvironment (TME) to M1, thereby activating anti-tumor related immune cells and inhibiting tumor growth. Moreover, the HA/M-Lipo CpG-P complexes showed a better tumor inhibitory effect than the HA/M-Lipo CpG or the HA/M-Lipo-P (monotherapy) treatment groups. Overall, HA/M-Lipo CpG-P complexes provide a promising co-delivery strategy for targeting tumors to improve the antitumor effect based on immune checkpoint blockade.

Comparative Study of a Series of 99mTc(CO)3 Mannosylated Dextran Derivatives for Sentinel Lymph Node Detection

Sentinel lymph node detection (SLND) is rapidly entering common practice in the management of patients with tumors. The introduction of mannose molecules to 99mTc-labeled dextrans, so far, showed that the sentinel node could trap these agents due to their recognition by the mannose receptors of lymph node macrophages. The current study aimed to synthesize, characterize, and biologically evaluate a series of mannosylated dextran derivatives labeled with 99mTc for potential use in SLND. The compounds were designed to have a dextran with a molecular weight of 10–500 kDa as a backbone, S-derivatized cysteines, efficient SNO chelators, and mannose moieties for binding to mannose receptors. They were successfully synthesized, thoroughly characterized using NMR techniques, and labeled with the fac-[99mTc(CO)3]+ synthon. Labeling with high yields and radiochemical purities was achieved with all derivatives. In vivo biodistribution and imaging studies demonstrated high uptake in the first lymph node and low uptakes in the following node and confirmed the ability to visualize the SLN. Among the compounds studied, 99mTc-D75CM demonstrated the most attractive biological features, and in combination with the high radiochemical yield and stability of the compound, its further evaluation as a new radiopharmaceutical for sentinel lymph node detection was justified.

A Novel Bivalent Mannosylated Targeting Ligand Displayed on Nanoparticles Selectively Targets Anti-Inflammatory M2 Macrophages.

Persistent activation of macrophages (MP)s into a proinflammatory M1 or anti-inflammatory M2 phenotype plays a role in several pathological conditions, including autoimmune diseases, fibrosis, infections, atherosclerosis and tumor development. The mannose receptor (MR, CD206), expressed at low levels on resting MPs and absent on M1 MPs, is highly expressed on M2 MPs, making it a potential target and drug delivery portal. Recently, we developed a novel, highly selective MR targeting ligand (MRTL), consisting of two mannose molecules separated by a monodisperse 12 unit poly(ethylene glycol) linker, to enhance the cellular uptake of polymeric nanocarriers. The feasibility of using the MRTL ligand for selectively targeting M2 MPs for intracellular delivery of nanoparticles (NPs) was investigated. Rat peritoneal MPs were differentiated into an M1 or M2 phenotype using IFN-γ and IL-4/IL-13, respectively. Expression of the M1 marker, inducible nitric oxide synthase (iNOS), and the M2 markers arginase (Arg)-1 and MR (at both the mRNA and protein levels) confirmed MP phenotypic activation. Resting, M1 and M2 MPs were treated with fluorescein isothiocyanate (FITC)-labeled MRTL or NPs displaying FITC-labeled MRTL at two surface densities (1 and 10%) and examined by confocal microscopy. Intracellular fluorescence was also quantified. Uptake of the MRTL was 2.4- and 11.8-fold higher in M2 MPs when compared to resting or M1 MPs, respectively, consistent with marker expression levels. Mannan, a competitive inhibitor of the MR, abrogated MRTL uptake. MRTL also co-localized with a fluid-phase endocytosis marker, further suggesting that uptake was mediated by MR-mediated endocytosis. Intracellular NP fluorescence was confirmed by flow cytometry and by confocal microscopy. MRTL-NPs accumulated intracellularly with no significant cell surface binding, suggesting efficient translocation. NPs displaying a low surface density (1%) of the MRTL exhibited significantly higher (2.3-fold) uptake into M2 MPs, relative to resting and M1 MPs. The 10% MRTL-NPs displayed greater uptake by M2 MPs when compared to resting and M1 MPs, but less uptake than 1% MRTL-NPs into M2 MPs. Control FITC-labeled plain NPs did not exhibit selective MP uptake. These studies demonstrate that M2 MPs are selectively targeted by NPs displaying a novel bivalent ligand that utilizes the MR as a target/portal for cell entry. This study also establishes the feasibility of the approach allowing for further investigation in vivo.

ALG9 Mutation Carriers Develop Kidney and Liver Cysts.

Mutations in PKD1 or PKD2 cause typical autosomal dominant polycystic kidney disease (ADPKD), the most common monogenic kidney disease. Dominantly inherited polycystic kidney and liver diseases on the ADPKD spectrum are also caused by mutations in at least six other genes required for protein biogenesis in the endoplasmic reticulum, the loss of which results in defective production of the PKD1 gene product, the membrane protein polycystin-1 (PC1). We used whole-exome sequencing in a cohort of 122 patients with genetically unresolved clinical diagnosis of ADPKD or polycystic liver disease to identify a candidate gene, ALG9, and in vitro cell-based assays of PC1 protein maturation to functionally validate it. For further validation, we identified carriers of ALG9 loss-of-function mutations and noncarrier matched controls in a large exome-sequenced population-based cohort and evaluated the occurrence of polycystic phenotypes in both groups. Two patients in the clinically defined cohort had rare loss-of-function variants in ALG9, which encodes a protein required for addition of specific mannose molecules to the assembling N-glycan precursors in the endoplasmic reticulum lumen. In vitro assays showed that inactivation of Alg9 results in impaired maturation and defective glycosylation of PC1. Seven of the eight (88%) cases selected from the population-based cohort based on ALG9 mutation carrier state who had abdominal imaging after age 50; seven (88%) had at least four kidney cysts, compared with none in matched controls without ALG9 mutations. ALG9 is a novel disease gene in the genetically heterogeneous ADPKD spectrum. This study supports the utility of phenotype characterization in genetically-defined cohorts to validate novel disease genes, and provide much-needed genotype-phenotype correlations.

Purification, structural characterization and anti-UVB irradiation activity of an extracellular polysaccharide from Pantoea agglomerans

Extracellular polysaccharide (EPS) produced by Pantoea agglomerans was purified for structural analysis and anti-UVB activity evaluation. The results showed that the EPS comprised of mannose and glucose in a ratio of 3:2. The molecular weight of EPS was estimated as 679 KDa. Fourier transform infrared spectrometry (FT-IR) showed that the EPS was composed of d-furanose without any substituent group. The structure of the EPS could be deduced as a repeated pentasaccharide arranged of three mannose molecules and two glucose molecules according to electrospray ionization mass spectrometry (ESI-MS) analysis and results mentioned above. The results also showed that the EPS attenuated UVB-induced cytotoxicity which was verified by morphology feature assay, down-regulated the expression of phosphor-JNK and active caspase3 significantly through MAPK pathway in UVB-irradiated HaCaT cells, and therefore protected the cells from apoptosis which could be identified by the lower apoptosis rate at low dose of UVB ray. In conclusion, the EPS as a macromolecule arranged by repeated pentasaccharide could protect HaCaT keratinocytes from UVB irradiation injury effectively, and the underlying mechanism may involve MAPK signaling pathway which contribute to apoptotic cell death. However, further studies on efficacy of the EPS in vivo are needed to determine.

The synthesis of a new macromolecule for the sentinel node detection: 99mTc-gly-mannosyl-dextran.

We aimed to design and synthesize a new macromolecule for sentinel node detection to improve the imaging quality and avoid possible adverse effect. The imaging of sentinel lymph node has been an important field in the nuclear medicine. A lot of imaging agents have been developed, including Tc-sulfer colloid, Tc-labeled dextrans and the latest Tc-DTPA-mannosyl-dextran. With the technology advanced, the imaging ability of the agents has been better and better. However, there are still some drawbacks. The new macromolecule agent was based on the dextran macromolecule backbone. Then the gly-gly-gly and mannose molecules were conjugated onto the backbone proportionally by targeting two different reaction sites. Once the new macromolecule was labelled with Tc, its imaging ability was tested by single-photon emission computed tomography scanning with Tc-sulfur colloid as the comparison. The average numbers of gly-gyl-gyl and mannosyl groups on the dextran backbone are determined to be ∼1: 2 per dextran. The average molecular diameter and molecular weight are measured to be 5.4±0.7 nm and 10 324 g/mol, respectively. The macromolecule is labelled by Tc with 93.2±2.4% radiochemical yield. The lymphatic imaging by single-photon emission computed tomography with the labeled compound showed no worse imaging ability but cost less time than the commercially available Tc-sulfur colloid. A new macromolecule imaging agent for sentinel node detection has been synthesized with better imaging ability and less imaging time cost.

Overview of the Structure⁻Function Relationships of Mannose-Specific Lectins from Plants, Algae and Fungi.

To date, a number of mannose-binding lectins have been isolated and characterized from plants and fungi. These proteins are composed of different structural scaffold structures which harbor a single or multiple carbohydrate-binding sites involved in the specific recognition of mannose-containing glycans. Generally, the mannose-binding site consists of a small, central, carbohydrate-binding pocket responsible for the “broad sugar-binding specificity” toward a single mannose molecule, surrounded by a more extended binding area responsible for the specific recognition of larger mannose-containing N-glycan chains. Accordingly, the mannose-binding specificity of the so-called mannose-binding lectins towards complex mannose-containing N-glycans depends largely on the topography of their mannose-binding site(s). This structure–function relationship introduces a high degree of specificity in the apparently homogeneous group of mannose-binding lectins, with respect to the specific recognition of high-mannose and complex N-glycans. Because of the high specificity towards mannose these lectins are valuable tools for deciphering and characterizing the complex mannose-containing glycans that decorate both normal and transformed cells, e.g., the altered high-mannose N-glycans that often occur at the surface of various cancer cells.

Glycosylated liposomes loading carbon dots for targeted recognition to HepG2 cells

It is important to obtain the targeted nanocarriers during cancer treatment. Herein, mannosylated liposomes encapsulating carbon dots (CDs) are provided for targeted recognition of liver cancer HepG2 cells, which is based on the specific interaction between D-mannose and glycoprotein on the surface of HepG2 cells. CDs were prepared by hydrothermal method. Then, they were encapsulated into liposomes by hydrophobic force. The encapsulation of CDs into liposomes increases their stability and fluorescence intensity. Furthermore, D-mannose can also be inserted into liposomes by the aldehyde amine reaction between aldehyde groups of mannose molecules and amino groups of liposomes. The obtained D-mannose-CDs-liposomes (Man-CDs-liposomes) exhibit selectively tracking and efficiently labelling for cancer cells. The work highlights the potential application of CDs for bioimaging and diagnostic.

Enrichment and characterization of a bacterial mixture capable of utilizing C-mannosyl tryptophan as a carbon source.

C-Mannosylation, a protein-modification found in various eukaryotes, involves the attachment of a single mannose molecule to selected tryptophan residues of proteins. Since C-mannosyl tryptophan (CMW) was detected in human urine, it is generally thought that CMW is not catabolized inside our body and instead is excreted via the urine. This paper reports enrichment of a bacterial consortium from soil that degrades CMW. The bacteria grew in minimal medium supplemented with CMW as the carbon source. Interestingly, even after successive clonal picks of individual colonies, several species were still present in each colony as revealed by 16S rRNA gene sequence analysis, indicating that a single species may not be responsible for this activity. A next generation sequencing (NGS) analysis was therefore carried out in order to determine which bacteria were responsible for the catabolism of CMW. It was found that a species of Sphingomonadaceae family, but not others, increased with simultaneous decrease of CMW in the media, suggesting that this species is most likely the one that is actively involved in the degradation of CMW.

The mechanism of reduced IgG/IgE-binding of β-lactoglobulin by pulsed electric field pretreatment combined with glycation revealed by ECD/FTICR-MS.

Bovine β-lactoglobulin (β-Lg) is a major allergen existing in milk and causes about 90% of IgE-mediated cow's milk allergies. Previous studies showed that pulsed electric field (PEF) treatment could partially unfold the protein, which may contribute to the improvement of protein glycation. In this study, the effect of PEF pretreatment combined with glycation on the IgG/IgE-binding ability and the structure of β-Lg was investigated. The result showed that PEF pretreatment combined with glycation significantly reduced the IgG and IgE binding abilities, which was attributed to the changes of secondary and tertiary structure and the increase in glycation sites and degree of substitution per peptide (DSP) value determined by electron capture dissociation Fourier transform ion cyclotron resonance mass spectrometry (ECD/FTICR-MS). Unexpectedly, glycation sites (K47, K91 and K135) added by two mannose molecules were identified in glycated β-Lg with PEF pretreatment. Moreover, the results indicated that PEF pretreatment at 25 kV cm-1 for 60 μs promoted the reduction of IgG/IgE-binding capacity by increasing the glycation degree of β-Lg, whereas single PEF treatment under the same conditions markedly enhanced the IgG/IgE-binding ability by partially unfolding the structure of β-Lg. The results suggested that ECD/FTICR-MS could help us to understand the mechanism of reduction in the IgG/IgE-binding of β-Lg by structural characterization at the molecular level. Therefore, PEF pretreatment combined with glycation may provide an alternative method for β-Lg desensitization.

Bioadhesive Bacterial Microswimmers for Targeted Drug Delivery in the Urinary and Gastrointestinal Tracts.

Bacteria‐driven biohybrid microswimmers (bacteriabots), which integrate motile bacterial cells and functional synthetic cargo parts (e.g., microparticles encapsulating drug), are recently studied for targeted drug delivery. However, adhesion of such bacteriabots to the tissues on the site of a disease (which can increase the drug delivery efficiency) is not studied yet. Here, this paper proposes an approach to attach bacteriabots to certain types of epithelial cells (expressing mannose on the membrane), based on the affinity between lectin molecules on the tip of bacterial type I pili and mannose molecules on the epithelial cells. It is shown that the bacteria can anchor their cargo particles to mannose‐functionalized surfaces and mannose‐expressing cells (ATCC HTB‐9) using the lectin–mannose bond. The attachment mechanism is confirmed by comparing the adhesion of bacteriabots fabricated from bacterial strains with or without type I pili to mannose‐covered surfaces and cells. The proposed bioadhesive motile system can be further improved by expressing more specific adhesion moieties on the membrane of the bacteria.