Akihiro Kishimura

Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) fabricated using a water-in-oil-in-water (w/o/w) double emulsion method can simultaneously encapsulate both hydrophilic proteins and hydrophobic drugs. This dual-loading ability of PLGA NPs is expected to be useful in allergen immunotherapy (AIT). We used the formulation to co-encapsulate a hydrophilic model antigen, ovalbumin (OVA), with hydrophobic drugs including rapamycin (Rapa), suberoylanilide hydroxamic acid (Saha) and bexarotene (Bexa). We successfully prepared NPs of approximately 100[ ]nm in diameter and co-encapsulated OVA and the hydrophobic drugs. The NPs remained in the intestinal tract for up to 4[ ]h following oral administration. We found that the NPs showed minimal release of the contents in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) and maintained stability without aggregation or degradation for 8[ ]h. These findings suggest that the NPs have the potential to serve as oral carriers for various hydrophobic drugs and antigens, while maintaining stability in gastrointestinal (GI) environments.

This study explores thermosensitive nanostructured coacervates formed by mixing ABA and AB block copolymers. Coacervates are liquid–liquid phase separation systems that can concentrate specific biomolecules, making them useful for biomedical applications such as sustained drug release. This study focuses on creating complex coacervates using ABA‐type triblock copolymers that can bridge isolated polyion complex (PIC) domains, enabling the formation of well‐ordered assemblies of polyethylene glycol (PEG)‐conjugated PIC nanoparticles. These coacervates exhibit mostly reversible responses to temperature changes and morphological hysteresis upon cooling, allowing for the controlled release of PIC micelles at physiological temperatures in the zero‐order kinetics. This study demonstrates that the degree of bridging of PIC domains can be tuned simply by adjusting the blend ratio of diblock to triblock copolymers, which affects their physical properties and responsiveness. Real‐time and snapshot observations of the assembling behaviors upon heating clarify the formation process of coacervates from both nano‐ and microscale viewpoints. The successful sustained release of a model protein, green fluorescent protein, is also confirmed to occur in a zero‐order manner. These findings suggest that these coacervates are promising depot formulations for nanomedicine, offering a novel model for studying intracellular biomolecular condensates and an intervention method for condensates.

This study explores the development of thermosensitive nanostructured coacervates formed by mixing ABA and AB block copolymers. Coacervates are liquid–liquid phase separation systems that can concentrate specific biomolecules, making them useful for biomedical applications such as sustained drug release. This study focuses on creating complex coacervates using ABA-type triblock copolymers that can bridge isolated polyion complex (PIC) domains, enabling the formation of well-ordered assemblies of polyethylene glycol (PEG)-conjugated PIC nanoparticles. These coacervates exhibit reversible responses to temperature changes and morphological hysteresis upon cooling, allowing for the controlled release of PIC micelles at physiological temperatures in the zero-order kinetics. This study demonstrates that the degree of bridging of PIC domains can be tuned simply by adjusting the blend ratio of diblock to triblock copolymers, which affects their physical properties and responsiveness. Real-time and snapshot observations of the assembling behaviors upon heating clarify the formation process of coacervates from both nano- and microscale viewpoints. The successful sustained release of a model protein, green fluorescent protein, is also confirmed to occur in a zero-order manner. These findings suggest that these coacervates are promising depot formulations for nanomedicine, offering a novel model for studying intracellular biomolecular condensates and an intervention method for condensates.

Researchers play a pivotal role as key actors in science communication. Therefore, it is imperative for academic institutions to support their activities. However, there are many uncertainties regarding activities by researcher and institutional support. Notably, researchers’ awareness and experience of these activities need to be clarified. Therefore, we conducted a questionnaire survey on researchers at Kyushu University in Japan to assess their awareness of and willingness to participate in science communication activities. The survey was conducted between 2021 and 2022. We sent a questionnaire to 2,336 researchers and received responses from 577 (24.7%). The survey revealed that the awareness of science communication was not very high (43%). Remarkably, awareness among medical, dental, and pharmaceutical researchers was relatively low. However, all field researchers recognized the importance of the activities and had a strong willingness to participate if given the opportunity. Furthermore, the results show that researchers in the humanities and social sciences had a relatively high awareness of promoting science communication in Japanese Science, Technology, and Innovation policy. Researchers over 40 years of age had more experience than researchers aged 20–39 years. Barriers such as time constraints and lack of regulation of personnel evaluation were reaffirmed.

We proposed a novel ligand for the interaction with human serum albumin (HSA) to extend the blood half-life of small molecular weight therapeutics. The ligand features an alkyl chain and an activated disulfide to allow binding to the hydrophobic pockets of HSA and the formation of disulfide to Cys34 of HSA, thereby minimizing the initial renal clearance. The dual nature of the ligand-HSA bonding was expected to give the ligand long blood retention. After 1 min of mixing with HSA, the ligand showed higher binding (1.7 times) than that of a control ligand (containing only activated disulfide). After intravenous injection to mice, the ligand half-lives were 1.6 and 9.2 times longer than those of control ligands with the active disulfide alone and with the alkyl chain alone, respectively. The proposed ligand has the potential to act as a platform for extending the half-life of small therapeutics in vivo.

Background: We have previously reported engineered macrophages (MacTriggers) that can accelerate the release of tumor necrosis factor-α in response to M2 polarization. MacTriggers are characterized by two original characteristics of macrophages: (1) migration to tumors; and (2) polarization to the M2 phenotype in tumors. Intravenously administered MacTriggers efficiently accumulated in the tumors and induced tumor-specific inflammation. This study reports a novel methodology for enhancing the anti-tumor effects of immune checkpoint inhibitors (ICIs). Results: In this study, we newly found that the intravenously administered MacTriggers in BALB/c mouse models upregulated the expression levels of immune checkpoint proteins, such as programmed cell death (PD)-1 in CD8⁺ T cells and PD-ligand 1 (PD-L1) in cancer cells and macrophages. Consequently, in two ICI-resistant tumor-inoculated mouse models, the combined administration of MacTrigger and anti-PD-1 antibody (aPD-1) synergistically inhibited tumor growth, whereas monotherapy with aPD-1 did not exhibit anti-tumor effects. This synergistic effect was mainly from aPD-1 enhancing the tumor-attacking ability of CD8⁺ T cells, which could infiltrate into the tumors following MacTrigger treatment. Importantly, no side effects were observed in normal tissues, particularly in the liver and spleen, indicating that the MacTriggers did not enhance the aPD-1 reactivity in normal tissues. This specificity was from the MacTriggers not polarizing to the M2 phenotype in normal tissues, thereby avoiding inflammation and increased PD-1/PD-L1 expression. MacTriggers could enhance aPD-1 reactivity only in tumors following tumor-specific inflammation induction. Conclusions: Our findings suggest that the MacTrigger and aPD-1 combination therapy is a novel approach for potentially overcoming the current low ICI response rates while avoiding side effects.