Modulation of immunogenicity of poly(sarcosine) displayed on various nanoparticle surfaces due to different physical properties.

Poly(sarcosine) displayed on polymeric micelle is reported to trigger a T cell-independent type2 reaction with B1a cells in the mice to produce IgM and IgG3 antibodies. In addition to polymeric micelle, three kinds of vesicles displaying poly(sarcosine) on surface were prepared here to evaluate the amounts and avidities of IgM and IgG3, which were produced in mice, to correlate them with physical properties of the molecular assemblies. The largest amount of IgM was produced after twice administrations of a polymeric micelle of 35 nm diameter (G1). On the other hand, the production amount of IgG3 became the largest after twice administrations of G3 (vesicle of 229 nm diameter) or G4 (vesicle of 85 nm diameter). The augmented avidity of IgG3 after the twice administrations compared with that at the single administration was the highest with G3. These differences in immune responses are discussed in terms of surface density of poly(sarcosine) chains, nanoparticle size, hydrophobic component of poly(L-lactic acid) or (Leu- or Val-Aib)n , and membrane elasticity of the nanoparticles. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Contact Allergy to Surfactants in a Hypoallergenic Liquid Cleanser.

: Surfactants are a relatively rare cause of allergic contact dermatitis (ACD) and testing patients to personal care products containing these ingredients has historically been difficult given their irritant properties. Using the semiopen technique, we were able to identify ACD to a hypoallergenic liquid cleanser in 2 patients who presented to our patch test clinic only months apart. Additional patch testing to individual ingredients led to subsequent identification of 3 novel surfactant allergens (sodium lauroyl sarcosinate, isostearamidopropyl morpholine lactate, and disodium lauroamphodiacetate). Only one of these allergens, sodium lauroyl sarcosinate, has previously been reported as a cause of ACD.

Paramagnetic nanoparticles as a platform for FRET-based sarcosine picomolar detection.

Herein, we describe an ultrasensitive specific biosensing system for detection of sarcosine as a potential biomarker of prostate carcinoma based on Förster resonance energy transfer (FRET). The FRET biosensor employs anti-sarcosine antibodies immobilized on paramagnetic nanoparticles surface for specific antigen binding. Successful binding of sarcosine leads to assembly of a sandwich construct composed of anti-sarcosine antibodies keeping the Förster distance (Ro) of FRET pair in required proximity. The detection is based on spectral overlap between gold-functionalized green fluorescent protein and antibodies@quantum dots bioconjugate (λex 400 nm). The saturation curve of sarcosine based on FRET efficiency (F604/F510 ratio) was tested within linear dynamic range from 5 to 50 nM with detection limit down to 50 pM. Assembled biosensor was then successfully employed for sarcosine quantification in prostatic cell lines (PC3, 22Rv1, PNT1A), and urinary samples of prostate adenocarcinoma patients.

Evasion from accelerated blood clearance of nanocarrier named as "Lactosome" induced by excessive administration of Lactosome.

BACKGROUND: Nanoparticle of Lactosome, which is composed of poly(l-lactic acid)-base depsipeptide with diameter of 35nm, accumulates in solid tumors by the enhanced permeability and retention (EPR) effect. However, a pharmacokinetic alteration of Lactosome was observed when Lactosome was repeatedly administered. This phenomenon is named as the Lactosome accelerated blood clearance (ABC) phenomenon. In this study, the effect of Lactosome dose on the ABC phenomenon was examined and discussed in terms of immune tolerance. METHODS: To tumor transplanted mice, Lactosome (0-350mg/kg) was administrated. At 7days after the first administration, indocyanine green (ICG)-labeled Lactosome (ICG-Lactosome, 0-350mg/kg) was injected. Near-infrared fluorescence imaging was performed, and biodistribution of ICG-Lactosome was evaluated. Further, the produced amounts of anti-Lactosome IgM were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: ICG-Lactosome accumulated in the tumor region when the first Lactosome dose exceeded over 150mg/kg. The amounts of anti-Lactosome IgM were inversely correlated with the first Lactosome doses. Even after establishment of the Lactosome ABC phenomenon with the first Lactosome dose as low as 5.0mg/kg, the Lactosome ABC phenomenon can be evaded apparently by dosing ICG-Lactosome over 50mg/kg regardless of anti-Lactosome IgM production. CONCLUSIONS: There are two different mechanisms for evasion from the Lactosome ABC phenomenon before and after its establishment. In either mechanism, however, the Lactosome ABC phenomenon can be evaded by excessive administration of Lactosome. GENERAL SIGNIFICANCE: Lactosome is a potential nanocarrier for drug and/or imaging agent delivery, which can be used for frequent administrations without significant pharmacokinetic alterations.

Demonstration of human, rye grass pollen extract-specific, helper and suppressor stimulating activity of modified allergens by effects on in vitro hapten-specific antibody production.

An in vivo system is described in which penicilloyl antibody was produced from peripheral leucocytes of a grass pollen-sensitive patient who had received penicillin therapy, by challenge of the cells with penicilloyl-grass pollen extract conjugate. Incubation of these leucocytes with a number of modified preparations of grass pollen extract with various T-cell-stimulating properties was shown to affect penicilloyl antibody production. Both chymotryptically fragmented rye grass pollen extract and a conjugate of f met-leu-phe and rye grass pollen extract enhanced penicilloyl-specific antibody similarly to the enhancement induced by unmodified extract, though at high concentration some suppression was seen. A conjugate of polysarcosine and rye grass pollen extract, previously shown to cause antibody suppression in mice, was similarly suppressive for penicilloyl-specific antibody. The system therefore shows potential for the evaluation of the effects of modified allergen treatment on antibody levels via T-cell mechanisms.

Suppression of murine IgE responses with amino acid polymer/allergen conjugates. IV. Suppressive activities in established IgE model systems.

Conjugates of poly-N-methylglycine (polysarcosine) and grass pollen extracts, previously found to be capable of suppressing immature IgE antibody responses in mice, were shown to be highly effective at inhibiting the capacity of immune splenocytes to produce a secondary response in sub-lethally irradiated recipient animals. Anamnestic IgE responses in mice primed without adjuvant were also suppressed, but the effects were modest and of short duration. The predictive value of murine models for selecting clinically appropriate specific IgE suppressive agents and treatment schedules that might be successfully employed for clinical use are discussed.

Suppression of murine IgE responses with amino acid polymer/allergen conjugates. I. Preparation of poly-(N-methylglycine)/grass pollen extract conjugates using 4-(methylmercapto)phenyl-succinimidyl succinate as coupling reagent.

A procedure utilising the latent activating potential of the 4-(methylmercapto)phenyl ester group has been developed for the controlled, reproducible preparation of macromolecular conjugates. This ester, as part of a succinyl-bridging group, was used to couple the water-soluble, amino acid polymer, poly-(N-methylglycine) (polysarcosine), via its N-terminal secondary amine, with the nucleophilic components of the aqueous extract of a mixture of grass pollens. The products exhibit a reproducible, antigen-specific suppressive effect on the in vivo synthesis of IgE in mice.

Suppression of murine IgE responses with amino acid polymer/allergen conjugates. II. Suppressive activities in adjuvant-induced IgE responses.

Treatment with conjugates of polysarcosine and grass pollen allergen extracts efficiently suppressed the induction of IgE responses in mice. The suppressive activity was shown to be allergen-specific and required covalent linking of the polysarcosine. Inhibitory effects could be overcome by booster injections of native allergen when these were given 3-4 weeks after treatment with conjugates. Administration of conjugates had only marginal effects on established IgE responses. The variance of these results with those of other studies on IgE suppression and the suitability of murine models for investigating reaginic antibody suppression are discussed.