Lacticaseibacillus rhamnosus Infective Endocarditis Complicated by Multifocal Mycotic Aneurysms in an Immunocompetent Patient: A Case Report.

Lactobacillaceae are generally considered low-pathogenicity organisms but can occasionally cause severe infections. We report a severe case of infective endocarditis caused by Lacticaseibacillus rhamnosus complicated by multifocal mycotic aneurysms in an immunocompetent patient who consumed probiotic drinks daily. He had a history of hypertension and aortic valve regurgitation.After starting antimicrobial treatment, the patient had rapid disease progression and required emergency surgery to prevent the rupture of two abdominal aneurysms. He subsequently experienced a rupture of an intracranial aneurysm, leading to a subarachnoid and intraventricular hemorrhage. This case highlights the potential severity of Lactobacillaceae infections, even in immunocompetent individuals with daily probiotic consumption. Interest in the health benefits of probiotics has grown in recent years, leading to increased global demand. The number of reported cases of Lactobacillaceae infections has also increased. When using probiotics, both the potential benefits and risks need to be considered, especially in susceptible individuals with predisposing conditions.

Enhancing Cell Aggregation and Migration via Double-Click Cross-Linking with Azide-Modified Hyaluronic Acid.

We present a novel approach to the formation of cell aggregates by employing click chemistry with water-soluble zwitterionic dibenzo cyclooctadiyne (WS-CODY) and azide-modified hyaluronic acid (HA-N3) as a linker to facilitate rapid and stable cell aggregation. By optimizing the concentrations of HA-N3 and WS-CODY, we achieved efficient cross-linking between azide-modified cell surfaces and HA-N3, generating cell aggregates within 10 min, and the resulting aggregates remained stable for up to 5 days, with cell viability maintained at approximately 80%. Systematic experiments revealed that a stoichiometric balance between HA-N3 and WS-CODY is important for effective cross-linking, highlighting the roles of both cell-surface azide modification and HA in the aggregate formation. We also investigated the genetic basis of altered cell behavior within these aggregates. Transcriptome analysis (RNA-seq) of aggregates postcultivation revealed a marked fluctuation of genes associated with 'cell migration' and 'cell adhesion', including notable changes in the expression of HYAL1, ICAM-1, CEACAM5 and RHOB. These findings suggest that HA-N3-mediated cell aggregation can induce intrinsic cellular responses that not only facilitate cell aggregate formation but also modulate cell-matrix interactions. We term this phenomenon 'chemo-resilience', The simplicity and efficacy of this click chemistry-based approach suggest it may have broad applicability for forming cell aggregates and modulating cell-matrix interactions in tissue engineering and regenerative medicine.

Hepatocyte Growth Factor DNA Aptamer for Prevention of Postoperative Peritoneal Adhesion via Enhancement of Fibrinolysis and Inhibition of Mesothelial Mesenchymal Transition.

Postoperative peritoneal adhesion (PPA) is a prevalent complication of abdominal surgery, posing a significant hindrance to postsurgical recovery. Although several strategies have been developed to alleviate and prevent adhesions, their efficacy remains unsatisfactory. For the first time, we studied the therapeutic effect and mechanism of our recently developed thermally stable oligonucleotide-based mimetics of hepatocyte growth factor (HGF DNA aptamer) to prevent PPA. The HGF DNA aptamer effectively inhibited canonical TGF-ß1 signaling transduction, partially suppressing mesothelial mesenchymal transition. Additionally, the aptamer, respectively, upregulated and downregulated the expression of tissue plasminogen activator and plasminogen activator inhibitor 1, thereby enhancing fibrinolytic activity. As a pleiotropic factor, the HGF DNA aptamer also enhanced the migratory and proliferative capacities of mesothelial cells. Finally, the aptamer demonstrated a higher level of effectiveness in preventing PPAs than the commercially available antiperitoneal adhesion barrier, Seprafilm. Due to its therapeutic benefits, excellent stability, biosafety, cost-effectiveness, and versatility, the HGF DNA aptamer demonstrates promise for preventing PPA in future clinical settings.

Transplantation of pancreatic beta-cell spheroids in mice via non-swellable hydrogel microwells composed of poly(HEMA-co-GelMA).

Pancreatic islet transplantation is an effective treatment for type I diabetes mellitus. However, many problems associated with pancreatic islet engraftment remain unresolved. In this study, we developed a hydrogel microwell device for islet implantation, fabricated by crosslinking gelatin-methacryloyl (GelMA) and 2-hydroxyethyl methacrylate (HEMA) in appropriate proportions. The fabricated hydrogel microwell device could be freeze-dried and restored by immersion in the culture medium at any time, allowing long-term storage and transport of the device for ready-to-use applications. In addition, due to its non-swelling properties, the shape of the wells of the device was maintained. Thus, the device allowed pancreatic ß cell lines to form spheroids and increase insulin secretion. Intraperitoneal implantation of the ß cell line-seeded GelMA/HEMA hydrogel microwell device reduced blood glucose levels in diabetic mice. In addition, they were easy to handle during transplantation and were removed from the transplant site without peritoneal adhesions or infiltration by inflammatory cells. These results suggest that the GelMA/HEMA hydrogel microwell device can go from spheroid and/or organoid fabrication to transplantation in a single step.

Moldable Tissue-Sealant Hydrogels Composed of In Situ Cross-Linkable Polyethylene Glycol via Thiol-Michael Addition and Carbomers.

Moldable tissue-sealant hydrogels were developed herein by combining the yield stress fluidity of a Carbomer and in situ cross-linking of 3-arm PEG-thiol (PEG-SH) and 4-arm PEG-acrylate (PEG-AC). The Carbomer was mixed with each PEG oligomer to form two aqueous precursors: Carbomer/PEG-SH and Carbomer/PEG-AC. The two hydrogel precursors exhibited sufficient yield stress (>100 Pa) to prevent dripping from their placement on the tissue surface. Moreover, these hydrogel precursors exhibited rapid restructuring when the shear strain was repeatedly changed. These rheological properties contribute to the moldability of these hydrogel precursors. After mixing these two precursors, they were converted from yield-stress fluids to chemically cross-linked hydrogels, Carbomer/PEG hydrogel, via thiol-Michael addition. The gelation time was 5.0 and 11.2 min at 37 and 25 °C, respectively. In addition, the Carbomer/PEG hydrogels exhibited higher cellular viability than the pure Carbomer. They also showed stable adhesiveness and burst pressure resistance to various tissues, such as the skin, stomach, colon, and cecum of pigs. The hydrogels showed excellent tissue sealing in a cecum ligation and puncture model in mice and improved the survival rate due to their tissue adhesiveness and biocompatibility. The Carbomer/PEG hydrogel is a potential biocompatible tissue sealant that surgeons can mold. It was revealed that the combination of in situ cross-linkable PEG oligomers and yield stress fluid such as Carbomer is effective for developing the moldable tissue sealant without dripping of its hydrogel precursors.

Development of Perfluoro Decalin/Fluorinated Polyimide Core-Shell Microparticles via SPG Membrane Emulsification Using Methyl Perfluoropropyl Ether Cosolvent.

Red blood cell-inspired perfluorocarbon-encapsulated core-shell particles have been developed for biomedical applications. Although the use of perfluorodecalin (FDC) is expected for core-shell particles owing to its high oxygen solubility, the low solubility of FDC in any organic solvent, owing to its fluorous properties, prevents its use in core-shell particles. In this study, a new cosolvent system composed of dichloromethane (DCM) and heptafluoropropyl methyl ether (HFPME) was found to dissolve both FDC and fluorinated polyimide (FPI) based on a systematic study using a phase diagram, achieving a homogeneous disperse phase for emulsification composed of oxygen-permeable FPI and oxygen-soluble FDC. Using this novel cosolvent system and Shirasu porous glass (SPG) membrane emulsification, FDC-encapsulated FPI shell microparticles were successfully prepared for the first time. In addition to oxygenation, demonstrated using hypoxia-responsive HeLa cells, the fabricated core-shell microparticles exhibited monodispersity, excellent stability, biocompatibility, and oxygen capacity.

Enhancing carbapenem antimicrobial dosing optimization: synergy of antimicrobial stewardship teams and ward-based clinical pharmacists.

Antimicrobial-product package inserts and insufficient staffing impede routine carbapenem monitoring in the inpatient setting in Japan. The collaboration between antimicrobial stewardship teams and clinical pharmacists was associated with a sustained improvement in carbapenem dosing optimization. Our findings could be of use to countries with inadequate monitoring of carbapenem antimicrobial use.

Injectable Extracellular Matrix-Inspired Hemostatic Hydrogel Composed of Hyaluronan and Gelatin with Shear-Thinning and Self-Healing.

Injectable ECM-inspired hydrogels composed of hyaluronic acid and gelatin are biocompatible and potentially useful for various medical applications. We developed injectable hydrogels composed of monoaldehyde-modified hyaluronic acid (HA-mCHO) and carbohydrazide-modified gelatin (GL-CDH), "HA/GL gel", whose ratios of HA-mCHO to GL-CDH were different. The hydrogels exhibited gelation times shorter than 3 s. In addition, the hydrogels showed strong shear-thinning and self-healing properties, mainly because of the dynamic covalent bonding of Schiff bases between HA-mCHO and GL-CDH. This hydrogel degraded in the mice's peritoneum for a week and showed excellent biocompatibility. Moreover, the hydrogel showed a higher breaking strength than fibrin glue in the lap shear test of porcine skin. Finally, the hydrogels decreased bleeding to as low as fibrin glue without using thrombin and fibrinogen in a mouse liver bleeding model in both single- and double-barreled syringe administrations. HA/GL gels have the potential for excellent biocompatibility and hemostasis in clinical settings.

AIbZIP/CREB3L4 Promotes Cell Proliferation via the SKP2-p27 Axis in Luminal Androgen Receptor Subtype Triple-Negative Breast Cancer.

Breast cancer ranks first in incidence and fifth in cancer-related deaths among all types of cancer globally. Among breast cancer, triple-negative breast cancer (TNBC) has few known therapeutic targets and a poor prognosis. Therefore, new therapeutic targets and strategies against TNBC are required. We found that androgen-induced basic leucine zipper (AIbZIP), also known as cyclic AMP-responsive element-binding protein 3-like protein 4 (CREB3L4), which is encoded by Creb3l4, is highly upregulated in a particular subtype of TNBC, luminal androgen receptor (LAR) subtype. We analyzed the function of AIbZIP through depletion of AIbZIP by siRNA knockdown in LAR subtype TNBC cell lines, MFM223 and MDAMB453. In AIbZIP-depleted cells, the proliferation ratios of cells were greatly suppressed. Moreover, G1-S transition was inhibited in AIbZIP-depleted cells. We comprehensively analyzed the expression levels of proteins that regulate G1-S transition and found that p27 was specifically upregulated in AIbZIP-depleted cells. Furthermore, we identified that this p27 downregulation was caused by protein degradation modulated by the ubiquitin-proteasome system via F-box protein S-phase kinase-associated protein 2 (SKP2) upregulation. Our findings demonstrate that AIbZIP is a novel p27-SKP2 pathway-regulating factor and a potential molecule that contributes to LAR subtype TNBC progression. IMPLICATIONS: This research shows a new mechanism for the proliferation of LAR subtype TNBC regulated by AIbZIP, that may provide novel insight into the LAR subtype TNBC progression and the molecular mechanisms involved in cell proliferation.

Injectable, shear-thinning, photocrosslinkable, and tissue-adhesive hydrogels composed of diazirine-modified hyaluronan and dendritic polyethyleneimine.

In the present study, we report the first synthesis of diazirine-modified hyaluronic acid (HA-DAZ). In addition, we also produced a precursor polymer solution composed of HA-DAZ and dendritic polyethyleneimine (DPI) that showed strong shear-thinning properties. Furthermore, its viscosity was strongly reduced (i.e., from 5 × 105 mPa s at 10-3 s-1 to 6 × 101 mPa s at 103 s-1), substantially, which enhanced solution injectability using a 21 G needle. After ultraviolet irradiation at 365 nm and 6 mW cm-2, the HA-DAZ/DPI solution achieved rapid gelation, as measured using the stirring method, and its gelation time decreased from 200 s to 9 s as the total concentrations of HA-DAZ and DPI increased. Following UV irradiation, the storage modulus increased from 40 to 200 Pa. In addition, reversible sol-gel transition and self-healing properties were observed even after UV irradiation. This suggests that the HA-DAZ/DPI hydrogel was crosslinked in multiple ways, i.e., via covalent bonding between the diazirine and amine groups and via intermolecular interactions, including hydrogen bonding, electrostatic interactions, and hydrophobic interactions. A lap shear test showed that the HA-DAZ/DPI hydrogel exhibited strong adhesiveness as a fibrin glue following UV irradiation. Finally, the HA-DAZ/DPI hydrogel showed higher tissue reinforcement than fibrin glue in an ex vivo burst pressure test of the porcine esophageal mucosa.

Injectable, Shear-Thinning, Self-Healing, and Self-Cross-Linkable Benzaldehyde-Conjugated Chitosan Hydrogels as a Tissue Adhesive.

Benzaldehyde-conjugated chitosan (CH-CBA) was synthesized by a coupling reaction between chitosan (CH) and carboxybenzaldehyde (CBA). The pH-sensitive self-cross-linking can be achieved through the Schiff base reaction. The degree of substitution (DS) of CH-CBA was controlled at 1.4-12.7% by optimizing the pH and reagent stoichiometry. The dynamic Schiff base linkages conferred strong shear-thinning and self-healing properties to the hydrogels. The viscosity of the 2 wt/v % CH-CBA hydrogel decreased from 5.3 × 107 mPa·s at a shear rate of 10-2 s-1 to 2.0 × 103 mPa·s at 102 s-1 at pH 7.4. The CH-CBA hydrogel exhibited excellent biocompatibility in vitro and in vivo. Moreover, the hydrogel adhered strongly to porcine small intestine, colon, and cecum samples, comparable to commercial fibrin glue, and exhibited effective in vivo tissue sealing in a mouse cecal ligation and puncture model, highlighting its potential as a biomaterial for application in tissue adhesives, tissue engineering scaffolds, etc.

Fabrication of Drug-Loaded Torus-Shaped Alginate Microparticles and Kinetic Analysis of Their Drug Release.

We fabricated drug-loaded, microsized, and torus-shaped alginate microparticles (TSMs) by vortex-ring freezing (VRF), utilizing vortex ring formation and ionic cross-linking. The equivalent outer diameter of the TSMs was ca. 200 µm. Several model drugs, such as doxorubicin, heparin, lysozyme, and several dextran derivatives, have been successfully loaded into TSMs. Because the TSMs were fragile due to the limitation of the process conditions of the VRF, drug-loaded TSMs were subsequently cross-linked via "post-cross-linking" with CaCl2, SrCl2, or BaCl2 to increase the cross-linking density of the alginate matrix, thereby enhancing the stability of dextran (Dex)-loaded TSMs (Dex-TSMs) and enabling the sustained release of natural Dex of 10, 70, or 150 kDa and cationic or anionic Dex at a physiological pH. The release kinetics of Dexs showed molecular weight and charge dependence; a relatively dense network of the alginate matrix of post-cross-linked TSMs resulted in the sustained release of Dexs with high molecular weights, heparin, and lysozyme for up to 7 days in the release test. Furthermore, the solute diffusivities of the dextran derivatives in the bulk alginate matrix were measured by using fluorescence correlation spectroscopy, which supported the release kinetics of TSMs. Drug-loaded TSMs have potential as drug carriers for biopharmaceuticals, such as proteins.

Prevention of esophageal stenosis via in situ cross-linkable alginate/gelatin powder in a new submucosal exfoliation model in rats.

Endoscopic submucosal dissection (ESD) for the treatment of esophageal mucosal lesions often leads to postoperative stenosis, causing difficulty in swallowing, known as dysphagia. In this study, we developed an in situ cross-linkable powder composed of alginate, gelatin, transglutaminase (TG), and calcium chloride ions (Ca2+), which can be administered through a 1.5 m-long and 3.2 mm-diameter endoscopic instrument channel. The powdered mixture of alginate and gelatin quickly formed a hydrogel by absorbing body fluids and was cross-linked by TG and Ca2+, which adhered ex vivo to porcine submucosal layers for over 2 weeks. In addition, we developed a new submucosal exfoliation model in rats that induced severe stenosis, similar to the ESD-induced stenosis models in clinical practice. When administered to the new rat model, the powder system effectively reduced the severity of esophageal stenosis based on body weight change monitoring, anatomical findings, and histological analysis. The body weight of the rats was maintained at the initial weight on postoperative day 14 (POD14), and epithelialization on POD7 and 14 improved to almost 100%. Additionally, collagen accumulation and the number of α-SMA-positive cells decreased due to powder administration. Therefore, these findings indicate that the in situ cross-linkable powder can prevent esophageal stenosis after ESD.

Optimization of physical microenvironment to maintain the quiescence of human induced pluripotent stem cell-derived hepatic stellate cells.

Hepatic stellate cells (HSCs) play a crucial role in liver fibrosis by producing excessive extracellular matrix (ECM) following chronic inflammation. However, studying HSC function has been challenging due to the limited availability of primary human quiescent HSCs (qHSCs) in vitro, and the fact that primary qHSCs quickly activate when cultured on plastic plates. Advances in stem cell technology have allowed for the generation of qHSCs from human induced pluripotent stem cells (hiPSCs) with the potential to provide an unlimited source of cells. However, differentiated quiescent-like HSCs (iqHSCs) also activate spontaneously on conventional plastic plates. In this study, we generated iqHSCs from hiPSCs and developed a culture method to maintain such iqHSCs in a lowly activated state for up to 5 days by optimizing their physical culture microenvironment. We observed that three-dimensional (3D) culture of iqHSCs in soft type 1 collagen hydrogels significantly inhibited their spontaneous activation in vitro while maintaining their ability to convert to activated state. Activation of iqHSC was successfully modeled by stimulating them with the fibrotic cytokine TGFß1. Hence, our culture method can be used to generate HSCs with functions comparable to those in a healthy liver, facilitating the development of accurate in vitro liver models for identifying novel therapeutic agents.

Impact of cell cycle on repair of ruptured nuclear envelope and sensitivity to nuclear envelope stress in glioblastoma.

The nuclear envelope (NE) is often challenged by various stresses (known as "NE stress"), leading to its dysfunction. Accumulating evidence has proven the pathological relevance of NE stress in numerous diseases ranging from cancer to neurodegenerative diseases. Although several proteins involved in the reassembly of the NE after mitosis have been identified as the NE repair factors, the regulatory mechanisms modulating the efficiency of NE repair remain unclear. Here, we showed that response to NE stress varied among different types of cancer cell lines. U251MG derived from glioblastoma exhibited severe nuclear deformation and massive DNA damage at the deformed nuclear region upon mechanical NE stress. In contrast, another cell line derived from glioblastoma, U87MG, only presented mild nuclear deformation without DNA damage. Time-lapse imaging demonstrated that repairing of ruptured NE often failed in U251MG, but not in U87MG. These differences were unlikely to have been due to weakened NE in U251MG because the expression levels of lamin A/C, determinants of the physical property of the NE, were comparable and loss of compartmentalization across the NE was observed just after laser ablation of the NE in both cell lines. U251MG proliferated more rapidly than U87MG concomitant with reduced expression of p21, a major inhibitor of cyclin-dependent kinases, suggesting a correlation between NE stress response and cell cycle progression. Indeed, visualization of cell cycle stages using fluorescent ubiquitination-based cell cycle indicator reporters revealed greater resistance of U251MG to NE stress at G1 phase than at S and G2 phases. Furthermore, attenuation of cell cycle progression by inducing p21 in U251MG counteracted the nuclear deformation and DNA damage upon NE stress. These findings imply that dysregulation of cell cycle progression in cancer cells causes loss of the NE integrity and its consequences such as DNA damage and cell death upon mechanical NE stress.

Recent advances in micro-sized oxygen carriers inspired by red blood cells.

Supplementing sufficient oxygen to cells is always challenging in biomedical engineering fields such as tissue engineering. Originating from the concept of a 'blood substitute', nano-sized artificial oxygen carriers (AOCs) have been studied for a long time for the optimization of the oxygen supplementation and improvement of hypoxia environments in vitro and in vivo. When circulating in our bodies, micro-sized human red blood cells (hRBCs) feature a high oxygen capacity, a unique biconcave shape, biomechanical and rheological properties, and low frictional surfaces, making them efficient natural oxygen carriers. Inspired by hRBCs, recent studies have focused on evolving different AOCs into microparticles more feasibly able to achieve desired architectures and morphologies and to obtain the corresponding advantages. Recent micro-sized AOCs have been developed into additional categories based on their principal oxygen-carrying or oxygen-releasing materials. Various biomaterials such as lipids, proteins, and polymers have also been used to prepare oxygen carriers owing to their rapid oxygen transfer, high oxygen capacity, excellent colloidal stability, biocompatibility, suitable biodegradability, and long storage. In this review, we concentrated on the fabrication techniques, applied biomaterials, and design considerations of micro-sized AOCs to illustrate the advances in their performances. We also compared certain recent micro-sized AOCs with hRBCs where applicable and appropriate. Furthermore, we discussed existing and potential applications of different types of micro-sized AOCs.

Prospective applications of two-dimensional materials beyond laboratory frontiers: A review.

The development of nanotechnology has been advancing for decades and gained acceleration in the 21st century. Two-dimensional (2D) materials are widely available, giving them a wide range of material platforms for technological study and the advancement of atomic-level applications. The design and application of 2D materials are discussed in this review. In order to evaluate the performance of 2D materials, which might lead to greater applications benefiting the electrical and electronics sectors as well as society, the future paradigm of 2D materials needs to be visualized. The development of 2D hybrid materials with better characteristics that will help industry and society at large is anticipated to result from intensive research in 2D materials. This enhanced evaluation might open new opportunities for the synthesis of 2D materials and the creation of devices that are more effective than traditional ones in various sectors of application.

p53-independent tumor suppression by cell-cycle arrest via CREB/ATF transcription factor OASIS.

CREB/ATF transcription factor OASIS/CREB3L1 is upregulated in long-term-cultured astrocytes undergoing cell-cycle arrest due to loss of DNA integrity by repeated replication. However, the roles of OASIS in the cell cycle remain unexplored. We find that OASIS arrests the cell cycle at G2/M phase after DNA damage via direct induction of p21. Cell-cycle arrest by OASIS is dominant in astrocytes and osteoblasts, but not in fibroblasts, which are dependent on p53. In a brain injury model, Oasis-/- reactive astrocytes surrounding the lesion core show sustained growth and inhibition of cell-cycle arrest, resulting in prolonged gliosis. We find that some glioma patients exhibit low expression of OASIS due to high methylation of its promoter. Specific removal of this hypermethylation in glioblastomas transplanted into nude mice by epigenomic engineering suppresses the tumorigenesis. These findings suggest OASIS as a critical cell-cycle inhibitor with potential to act as a tumor suppressor.

pH responsive cationic guar gum-borate self-healing hydrogels for muco-adhesion.

We developed a new muco-adhesive hydrogel composed of cationic guar gum (CGG) and boric acid (BA). The CGG-BA precursor solution of 0.5-2% w/v concentration exhibited fluidity at low pH (3-5), while gelation occurred within 1 min at physiological pH (7-8) conditions. Scanning electron microscopy and Fourier-transform infrared spectroscopy results confirmed the change in physical and chemical behavior, respectively, with change in pH. The pH-responsive self-healing ability was analyzed through microscopy and rheology. CGG-BA hydrogels showed good self-healing property at pH 7.4. The in vitro biocompatibility test of the hydrogel studied using NIH3T3 and NHEK cells showed that it was non-toxic at concentrations of CGG-BA below 2% w/v. Ex vivo mucoadhesive tests confirmed the hydrogel's potential for use as a muco-adhesive. Burst pressure tests were conducted using pig esophageal mucosa and the results showed that at pH 7.4, 1% w/v CGG-BA self-healable hydrogel resisted about 8 ± 2 kPa pressure, comparable to that of Fibrin glue. This was higher than that at solution (pH 5) and brittle gel (pH 10) conditions. To confirm the good adhesive strength of the self-healable hydrogels, lap shear tests conducted, resulted in adhesive strengths measured in the range of 1.0 ± 0.5-2.0 ± 0.6 kPa, which was also comparable to fibrin glue control 1.8 ± 0.6 kPa. Hydrogel weight measurements showed that 40-80% gel lasted under physiological conditions for 10 h. The results suggest that CGG-BA hydrogel has potential as a pH responsive mucosal protectant biomaterial.

Development of a Potassium-Ion-Responsive Star Copolymer with Controlled Aggregation/Dispersion Transition.

Stimuli-responsive star polymers are promising functional materials whose aggregation, adhesion, and interaction with cells can be altered by applying suitable stimuli. Among several stimuli assessed, the potassium ion (K+), which is known to be captured by crown ethers, is of considerable interest because of the role it plays in the body. In this study, a K+-responsive star copolymer was developed using a polyglycerol (PG) core and grafted copolymer arms consisting of a thermo-responsive poly(N-isopropylacrylamide) unit, a metal ion-recognizing benzo-18-crown-6-acrylamide unit, and a photoluminescent fluorescein O-methacrylate unit. Via optimization of grafting density and copolymerization ratio of grafted arms, along with the use of hydrophilic hyperbranched core, microsized aggregates with a diameter of 5.5 µm were successfully formed in the absence of K+ ions without inducing severe sedimentation (the lower critical solution temperature (LCST) was 35.6 °C). In the presence of K+ ions, these aggregates dispersed due to the shift in LCST (47.2 °C at 160 mM K+), which further induced the activation of fluorescence that was quenched in the aggregated state. Furthermore, macrophage targeting based on the micron-sized aggregation state and subsequent fluorescence activation of the developed star copolymers in response to an increase in intracellular K+ concentration were performed as a potential K+ probe or K+-responsive drug delivery vehicle.