Dal-Hee Min

Nickel has recently emerged as a promising catalytic center for single-atom catalysts, owing to its biological relevance, redox versatility, and favorable coordination chemistry. Herein, we report the synthesis of a multifunctional nanozyme (Ni/PEG-FA) comprising atomically dispersed nickel sites anchored on a nitrogen-doped carbon support. The nanozyme is functionalized with poly(ethylene glycol) to improve colloidal stability and biocompatibility, and further conjugated with folic acid to enable the selective targeting of cancer cells overexpressing folate receptors. Ni/PEG-FA exhibits dual enzyme-mimicking activity, catalyzing both peroxidase-like and superoxide dismutase-like reactions for efficient reactive oxygen species generation under physiological conditions. In addition, Ni/PEG-FA shows strong photothermal conversion upon near-infrared laser irradiation, enabling effective thermal ablation of tumor cells. In vitro and in vivo evaluations demonstrate that Ni/PEG-FA elicits synergistic antitumor effects by combining catalytic oxidative stress with photothermal therapy, with minimal systemic toxicity. These findings underscore the potential of Ni-based single-atom nanozymes as a safe and effective platform for reactive oxygen species–powered cancer therapy.

Most hospital-acquired infections originate from bacterial biofilms on implantable devices, where the extracellular polymeric substance (EPS) matrix protects microbes and promotes multidrug resistance (MDR). Preventing biofilm initiation, particularly bacterial adhesion and proliferation, offers an effective strategy to combat device-associated infections. However, developing biocompatible materials that combine antimicrobial and antiadhesive functions remains a challenge. Herein, we present a strategy to engineer antibiofilm hydrogels by incorporating antimicrobial peptoids (ampetoids) into a gelatin-based matrix with controlled supramolecular organization. By tuning the stoichiometric ratio between thiol-functionalized ampetoids and norbornene groups in the matrix, we controlled peptoid nanostructure within the hydrogel, where suppression of peptoid self-assembly proved critical for balancing antimicrobial activity, antiadhesive properties, and cytocompatibility. This molecular-level control enabled the hydrogels to inhibit biofilm formation by S. aureus and P. aeruginosa. These results highlight regulation of peptoid self-assembly within hydrogels as a promising approach for designing multifunctional antibiofilm coatings for contamination-prone medical devices.

A high-throughput graphene oxide-based fluorescence assay enables real-time monitoring of SARS-CoV-2 RdRp activity and rapid antiviral screening. Using this platform, we identify fingolimod as an RdRp inhibitor with validated antiviral effects.

Jun Seo Park, Dong Geon Lee, Dal-Hee Min and Sung Joong Lee. Exp Neurobiol -0001;0:. https://doi.org/10.5607/en25026

Glioblastoma (GBM) remains uniformly fatal despite maximal surgical resection, temozolomide chemotherapy, and radiotherapy. Within the GBM microenvironment, tumor-educated microglia and astrocytes adopt immunosuppressive M2-like and A2 phenotypes, respectively, which shield GBM cells from adaptive immune attack. In this review, we examine emerging adjuvant strategies designed to molecularly reprogram glial cells toward proinflammatory M1/A1 states, amplifying antitumor immunity. First, we summarize key aspects of GBM pathobiology and identify why conventional treatments fail to achieve durable control. Next, we dissect the signaling networks that govern glial phase states, including NF-κB, STAT3, IRF3, NLRP3, and cGAS–STING axes. We then provide a mechanism-centric analysis of pattern-recognition receptor (PRR) agonists, inflammasome modulators, and cyclic-dinucleotide STING agonists, integrating quantitative preclinical data with early clinical trial results. For each adjuvant, we distinguish between direct astrocytic engagement and indirect cytokine-mediated reprogramming. Modulation of glial phase states holds considerable promise for enhancing personalized vaccine efficacy and for converting immunologically “cold” GBM into a T cell–inflamed tumor. Consequently, targeting glial cell phase modulation is a highly attractive strategy for GBM immunotherapy, with the potential to maximize therapeutic benefit. Despite increasing interest in cancer immunotherapy, GBM remains one of the most challenging malignancies to treat due to its uniquely immunosuppressive brain microenvironment. While chemotherapy, radiotherapy, and checkpoint inhibitors have revolutionized treatment of GBM, these strategies have had limited success largely due to failure to control immunological memory and the dominant role of glial cells in immune evasion. Astrocytes and microglia in the GBM microenvironment undergo tumor-induced polarization toward immunosuppressive phenotypes, forming a barrier to effective T cell–mediated antitumor responses. Recent studies suggest that molecularly reprogramming glial cells toward proinflammatory states could recondition the tumor microenvironment (TME), enabling more effective immunotherapy. This review explores glial phase reprogramming as an emerging immunoadjuvant strategy with a focus on key molecular circuits, synthetic modulators, and translational implications.

This study evaluated the safety, tolerability, and pharmacokinetics of LEM‐S401, a novel siRNA therapeutic with DegradaBALL, a mesoporous silica nanoparticle‐based delivery system. LEM‐S401 is designed to deliver siRNA targeting connective tissue growth factor (CTGF) to fibroblasts for treating hypertrophic scars and keloids, both of which result from abnormal collagen proliferation. LEM‐S401, containing unmodified siRNA LEM‐17234 encapsulated in DegradaBALL nanoparticles, was administered subcutaneously to healthy adults in a randomized, double‐blind, placebo‐controlled, single‐ascending dose study. Safety and tolerability assessments included vital signs, adverse events (AEs), laboratory tests, and cytokine levels. Pharmacokinetic analysis of LEM‐17234 and silicon (Si), the primary component of DegradaBALL, was performed using blood samples collected at specified time points. LEM‐S401 demonstrated a favorable safety and tolerability profile with only mild, self‐resolving injection site reactions including pain and erythema. No systemic AEs were observed, and cytokine levels showed no significant changes between the treatment and placebo groups. Pharmacokinetic analysis revealed that LEM‐17234 was below the plasma detection limit, indicating no notable systemic exposure of siRNA, while Si showed no dose‐dependent systemic exposure, suggesting minimal systemic circulation of the mesoporous silica nanoparticles. These findings suggest DegradaBALL effectively encapsulates and delivers siRNA locally without significant systemic exposure. The novel DegradaBALL delivery system enables the stable and targeted delivery of siRNA, which presumably overcomes challenges related to siRNA instability and off‐target effects. LEM‐S401 has the potential to advance the treatment of fibrotic skin diseases such as keloids and hypertrophic scars by delivering siRNA directly to fibroblasts, thereby inhibiting excessive collagen production.Trial Registration: ClinicalTrials.gov identifier: NCT04707131. https://clinicaltrials.gov/study/NCT04707131?cond=NCT04707131&rank=1

The coronavirus disease (COVID-19) pandemic accelerated development of various vaccine platforms. Among them, mRNA vaccines played a crucial role in controlling the pandemic due to their swift development and efficacy against virus variants. Despite the success of these vaccines, recent studies highlight challenges in evaluating vaccine efficacy, especially in individuals with prior COVID-19 infection. Weakened neutralizing antibody responses after additional doses are observed in these populations, raising concerns about using neutralizing antibody titers as the sole immune correlate of protection. While neutralizing antibodies remain the primary endpoint in immunogenicity trials, they may not fully capture the immune response in populations with widespread prior infection or vaccination. This review explores reduced neutralizing antibody responses in previously infected individuals, and their impact on vaccine efficacy evaluation. It also offers recommendations for improving efficacy assessment, stressing incorporation of additional immune markers such as cell-mediated immunity to enable more comprehensive understanding of vaccine-induced immunity.