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The non-enzymatic kinetic resolution of primary amines via enantioselective N-acylation with acyl chlorides was accomplished for the first time by using the selective sequestration of one enantiomer within a supramolecular cyclodextrin (CD) nanocapsule in nonpolar solvents. In addition, the first example of a crystalline structure for an inclusion complex between an acyl chloride and a CD derivative is reported.

One of the major challenges in cell-based cardiac regenerative medicine is the in vitro construction of three-dimensional (3D) tissues consisting of induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) and a blood vascular network supplying nutrients and oxygen throughout the tissue after implantation. We have successfully built a vascularized iPSC-CM 3D-tissue using our validated cell manipulation technique. In order to evaluate an availability of the 3D-tissue as a biomaterial, functional morphology of the tissues was examined by light and transmission electron microscopy through their implantation into the rat infarcted heart. Before implantation, the tissues showed distinctive myofibrils within iPSC-CMs and capillary-like endothelial tubes, but their profiles were still like immature. In contrast, engraftment of the tissues to the rat heart led the iPSC-CMs and endothelial tubes into organization of cell organelles and junctional apparatuses and prompt development of capillary network harboring host blood supply, respectively. A number of capillaries in the implanted tissues were derived from host vascular bed, whereas the others were likely to be composed by fusion of host and implanted endothelial cells. Thus, our vascularized iPSC-CM 3D-tissues may be a useful regenerative paradigm which will require additional expanded and long-term studies.

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.OBJECTIVES: To examine effects of topical mucosal administration of γ-PGA-Phe NPs as a potentially combined antigen delivery system and adjuvant.METHODS: γ-PGA-Phe NPs were administered on rat middle ear mucosa in a sham-controlled design and the response was monitored, focusing on soluble markers in mucosal surface liquids and on overall histopathology.RESULTS: γ-PGA-Phe NPs produced a dose- and time-dependent inflammatory response characterized by generation of proinflammatory cytokines (IL-1α, IL-1β, IL-6, MIP-1α, and TNF-α) and associated histopathological changes.

『バイオマテリアル研究の最前線』, "The advanced research of biomaterials ", 5-2 高分子系バイオマテリアル, 第5章 セラミックス系・高分子系バイオマテリアル研究の最前線

The non-enzymatic kinetic resolution of primary amines via enantioselective N-acylation with acyl chlorides was accomplished for the first time by using the selective sequestration of one enantiomer within a supramolecular cyclodextrin (CD) nanocapsule in nonpolar solvents. In addition, the first example of a crystalline structure for an inclusion complex between an acyl chloride and a CD derivative is reported., journal article

Agonistic anti-CD40 monoclonal antibodies (mAbs) hold great potential for cancer immunotherapy. However, systemic administration of anti-CD40 mAbs can be associated with severe side effects, such as cytokine release syndrome and liver damage. With the aim to increase the immunostimulatory potency as well as to achieve a local drug retention of anti-CD40 mAbs, we linked an agonistic mAb to immune activating amphiphilic poly(gamma-glutamic acid) nanoparticles (gamma-PGA NPs). We demonstrate that adsorption of anti-CD40 mAb to gamma-PGA NPs (anti-CD40-NPs) improved the stimulatory capacity of the CD40 agonist, resulting in upregulation of costimulatory CD80 and CD86 on antigen-presenting cells, as well as IL-12 secretion. Interestingly, anti-CD40-NP5 induced strong synergistic proliferative effects in B cells, possibly resulting from a higher degree of CD40 multimerization, enabled by display of multiple anti-CD40 mAbs on the NPs. In addition, local treatment with anti-CD40-NPs, compared to only soluble CD40 agonist, resulted in a significant reduction in serum levels of IL-6, IL-10, IL-12 and TNF-alpha in a bladder cancer model. Taken together, our results suggest that anti-CD40-NPs are capable of synergistically enhancing the immunostimulatory effect induced by the CD40 agonist, as well as minimizing adverse side effects associated with systemic cytokine release. This concept of nanomedicine could play an important role in localized immunotherapy of cancer.

特集 バイオポリマーインターフェイス－生体分子が拓く新たな高分子界面－

identifier:https://dspace.jaist.ac.jp/dspace/handle/10119/4959

The objective of the present study was to prepare nanoparticles composed of poly (γ-glutamic acid) (γ-PGA) and L-phenylalanine ethylester (L-PAE) in order to evaluate the possibility of using these nanoparticles as protein carriers. Novel amphiphilic graft copolymers composed of γ-PGA as the hydrophilic backbone and L-PAE as the hydrophobic segment were successfully synthesized by grafting L-PAE to γ-PGA using water-soluble carbodiimide (WSC). Due to their amphiphilic properties, the γ-PGA-graft-L-PAE copolymers were able to form nanoparticles. The size of the γ-PGA nanoparticles was measured by photon correlation spectroscopy (PCS), and showed a narrow monodispersed size distribution with a mean diameter ranging from 150 to 200 nm. The solvents selected to prepare the γ-PGA nanoparticles by a precipitation and dialysis method affected the particle size distribution. To evaluate the feasibility of vehicles for these proteins, we prepared protein-loaded γ-PGA nanoparticles by surface immobilization and encapsulation methods. Ovalbumin (OVA) was used as a model protein, and was immobilized onto the γ-PGA nanoparticles or encapsulated into the inner core of these nanoparticles. Moreover, these OVA-encapsulated γ-PGA nanoparticles could be preserved by freeze-drying process. The results of cytotoxicity tests showed that the γ-PGA and γ-PGA nanoparticles did not cause any relevant cell damage. It is expected that biodegradable γ-PGA nanoparticles can immobilize proteins, peptides, plasmid DNA and drugs onto their surfaces and/or into the nanoparticles. These nanoparticles are potentially useful in pharmaceutical and biomedical applications.

Uniform polymeric nanoparticles with various morphologies of projection coronas like the viruses in the coronavirus group have been formed by the self-organization of macromolecular chains polymerizing in a dispersion system of styrene (St), acrylonitrile (AN) and poly(ethylene glycol) monomethacrylate (PEGm) in a polar solvent (water/ethanol). An increase in the water composition reduced the crystallization degree of AN units, resulting in a variety of the nanoparticle morphology such as the increased particle size, the reduced projection size, the increased projection number, and the decreased inter-projection distance. The difference in the projection morphology strongly affected a dispersibility in water., identifier:https://dspace.jaist.ac.jp/dspace/handle/10119/4931

A novel thermotropic liquid crystalline biocopolymer, poly{4-hydroxycinnamic acid (4HCA: coumaric acid)-co-lithocholic acid (LCA)}, was synthesized by a thermal polycondensation of 4HCA and LCA. When the LCA molar composition of P(4HCA-co-LCA)) was 0, 5, 7, 23, 27, and 45 mol%, the copolymers showed a nematic liquid-crystalline phase. The melting point of the copolymers was 120-250 oC depending on the LCA composition, and showed a maximum at 7 mol%. Wide angle X-ray diffraction (WAXD) analysis showed a typical diffraction pattern of a hexagonal arrangement for 0, 7, 23, and 27 mol% LCA molar composition, which were cooled from a nematic melt. The other polymers showed no distinct diffraction. In particular, the copolymer of 7 mol% LCA molar composition showed four distinct diffractions corresponding to spacings with a reciprocal ratio of 1, 3^<0.5>, 2, and 7^<0.5>, indicating the highest structural ordering of all copolymers prepared here. The results of the cell adhesion and static contact angle tests suggest that the 7 mol% LCA molar composition copolymer had the highest hydrophobicity and cell adhesion ability, which was easily controlled by altering in feed. We conclude that the structural ordering may have a significant correlation with cell adhesion activity., identifier:https://dspace.jaist.ac.jp/dspace/handle/10119/4932

A novel thermotropic liquid crystalline biocopolymer, poly{4-hydroxycinnamic acid (4HCA: coumaric acid)-co-lithocholic acid (LCA)}, was synthesized by a thermal polycondensation of 4HCA and LCA. When the LCA molar composition of P(4HCA-co-LCA)) was 0, 5, 7, 23, 27, and 45 mol%, the copolymers showed a nematic liquid-crystalline phase. The melting point of the copolymers was 120-250 oC depending on the LCA composition, and showed a maximum at 7 mol%. Wide angle X-ray diffraction (WAXD) analysis showed a typical diffraction pattern of a hexagonal arrangement for 0, 7, 23, and 27 mol% LCA molar composition, which were cooled from a nematic melt. The other polymers showed no distinct diffraction. In particular, the copolymer of 7 mol% LCA molar composition showed four distinct diffractions corresponding to spacings with a reciprocal ratio of 1, 3^<0.5>, 2, and 7^<0.5>, indicating the highest structural ordering of all copolymers prepared here. The results of the cell adhesion and static contact angle tests suggest that the 7 mol% LCA molar composition copolymer had the highest hydrophobicity and cell adhesion ability, which was easily controlled by altering in feed. We conclude that the structural ordering may have a significant correlation with cell adhesion activity.

Uniform polymeric nanoparticles with various morphologies of projection coronas like the viruses in the coronavirus group have been formed by the self-organization of macromolecular chains polymerizing in a dispersion system of styrene (St), acrylonitrile (AN) and poly(ethylene glycol) monomethacrylate (PEGm) in a polar solvent (water/ethanol). An increase in the water composition reduced the crystallization degree of AN units, resulting in a variety of the nanoparticle morphology such as the increased particle size, the reduced projection size, the increased projection number, and the decreased inter-projection distance. The difference in the projection morphology strongly affected a dispersibility in water.