1.The role of hydrophobicity in the disruption of erythrocyte membrane by nanoparticles composed of hydrophobically modified poly(γ-glutamic acid).
Shima F1, Akagi T, Akashi M. J Biomater Sci Polym Ed. 2014;25(2):203-10. doi: 10.1080/09205063.2013.848328. Epub 2013 Oct 18.
Polymeric nanoparticles (NPs) prepared from biocompatible polymers have been studied extensively as carriers for the targeted and controlled delivery of antigens to develop safe and effective vaccines. Especially, the endosomal escape of antigens is essential for the induction of antigen-specific potent immune responses, and the NPs which can control the endosomal escape are urgently required. It has been reported that the hydrophobicity of polymers affected the interactions between the polymer and the membranes, but there have no reports about investigating the effect of the hydrophobicity of the NPs on the membrane disruptive property. In this study, we evaluated the effect of hydrophobicity of NPs on the membrane disruptive property for the first time. We prepared NPs composed of amphiphilic poly(γ-glutamic acid) (γ-PGA) with various grafting degrees of hydrophobic backbone (43-71%), and evaluated the membrane disruptive property. These NPs showed membrane disruptive activity only at the endosomal pH range, and this activity was dependent on the hydrophobicity of γ-PGA.
2.Induction of potent adaptive immunity by the novel polyion complex nanoparticles.
Uto T1, Akagi T2, Akashi M2, Baba M3. Clin Vaccine Immunol. 2015 May;22(5):578-85. doi: 10.1128/CVI.00080-15. Epub 2015 Mar 25.
The development of effective and simple methods of vaccine preparation is desired for the prophylaxis and treatment of a variety of infectious diseases and cancers. We have created novel polyion complex (PIC) nanoparticles (NPs) composed of amphiphilic anionic biodegradable poly(γ-glutamic acid) (γ-PGA) and cationic polymers as a vaccine adjuvant. PIC NPs can be prepared by mixing γ-PGA-graft-l-phenylalanine ethylester (γ-PGA-Phe) polymer with cationic polymer in phosphate-buffered saline. We examined the efficacy of PIC NPs for antigen delivery and immunostimulatory activity in vitro and in vivo. PIC NPs enhanced the uptake of ovalbumin (OVA) by dendritic cells (DCs) and subsequently induced DC maturation. The immunization of mice with OVA-carrying PIC NPs induced potent and antigen-specific cellular and humoral immunity. Since PIC NPs can be created with water-soluble anionic γ-PGA-Phe and a cationic polymer by simple mixing in the absence of any organic solvents, PIC NPs may have potential as a novel candidate for an effective antigen carrier and vaccine adjuvant.
3.Amino Acid-based fluorescent chiral ionic liquid for enantiomeric recognition.
Bwambok DK1, Challa SK, Lowry M, Warner IM. Anal Chem. 2010 Jun 15;82(12):5028-37. doi: 10.1021/ac9027774.
We report on the synthesis and characterization of a new fluorescent chiral ionic liquid (FCIL), l-phenylalanine ethyl ester bis(trifluoromethane) sulfonimide (l-PheC(2)NTf(2)), capable of serving simultaneously as solvent, chiral selector, and fluorescent reporter in chiral analytical measurements. Enantiomers of different analytes, including fluorescent and nonfluorescent compounds, with a variety of structures were shown to induce wavelength- and analyte-dependent changes in the fluorescence intensity of this FCIL. This system may provide both chemo- and enantioselectivity toward multiple analytes simultaneously. The newly synthesized FCIL, derived from commercially available l-phenylalanine ethyl ester chloride and lithium bis(trifluoromethane) sulfonamide, was obtained as liquid at room temperature and is stable to thermal decomposition up to 270 degrees C. Absorption and fluorescence properties of neat l-PheC(2)NTf(2) were complex.
4.Amphiphilic γ-PGA nanoparticles administered on rat middle ear mucosa produce adjuvant-like immunostimulation in vivo.
Nilsson JS1, Broos S, Akagi T, Akashi M, Hermansson A, Cayé-Thomasen P, Lindstedt M, Greiff L. Acta Otolaryngol. 2014 Oct;134(10):1034-41. doi: 10.3109/00016489.2014.918278.
CONCLUSION: Amphiphilic biodegradable nanoparticles (NPs) composed of poly(γ-glutamic acid) conjugated with L-phenylalanine ethylester (γ-PGA-Phe NPs) applied on the rat middle ear mucosa produce an inflammatory type 1 response. The observation is of relevance for the use of γ-PGA-Phe NPs as a concomitant antigen delivery system and adjuvant measure in the context of vaccinations.