There is an incontestable need for improved treatment modality for glioblastoma due to its extraordinary resistance to traditional chemoradiation therapy. Boron neutron capture therapy (BNCT) may play a role in the future. We designed and synthesized a ¹⁰B-boronated derivative of temozolomide, TMZB. BNCT was carried out with a total neutron radiation fluence of 2.4 ± 0.3 × 10¹¹ n/cm². The effects of TMZB in BNCT were measured with a clonogenic cell survival assay in vitro and PET/CT imaging in vivo. Then, ¹⁰B-boronated phenylalanine (BPA) was tested in parallel with TMZB for comparison. The IC50 of TMZB for the cytotoxicity of clonogenic cells in HS683 was 0.208 mM, which is comparable to the IC50 of temozolomide at 0.213 mM. In BNCT treatment, 0.243 mM TMZB caused 91.2% ± 6.4% of clonogenic cell death, while 0.239 mM BPA eliminated 63.7% ± 6.3% of clonogenic cells. TMZB had a tumor-to-normal brain ratio of 2.9 ± 1.1 and a tumor-to-blood ratio of 3.8 ± 0.2 in a mouse glioblastoma model. BNCT with TMZB in this model caused 58.2% tumor shrinkage at 31 days after neutron irradiation, while the number for BPA was 35.2%. Therefore, by combining the effects of chemotherapy from temozolomide and radiotherapy with heavy charged particles from BNCT, TMZB-based BNCT exhibited promising potential for therapeutic applications in glioblastoma treatment.

Enzymes play a significant role in mediating inflammatory and immune responses in periodontitis. Effective diagnosis, timely treatment, and continuous management of periodontal enzymes are essential to prevent undesirable consequences; however, this remains a significant challenge. Nanoparticles (NPs) have attracted significant attention in biomedicine because of their advantageous nanosized effects. NPs are conjugated with specific enzyme substrates at responsive sites that are triggered by periodontitis enzyme biomarkers, leading to functional or characteristic changes. In contrast, NPs with enzyme-mimetic activities exhibit catalytic activity, effectively destroying pathogenic biofilms and modulating the immune response in periodontitis. The unique properties of enzyme-targeting NPs have enabled the development of biosensors and fluorescent probes capable of identifying enzyme biomarkers associated with periodontitis. Enzyme-responsive and enzyme-mimetic NPs both exert therapeutic applications in the treatment of periodontitis. In this review, we provide a comprehensive overview of the enzymes associated with periodontitis, the mechanisms of enzyme-responsive and enzyme-mimetic NPs, recent advancements in the use of NPs for detecting these enzymes, and the therapeutic applications of NPs in targeting or mimicking enzyme functions. We also discuss the challenges and prospects of using NPs in the diagnosis and treatment of periodontitis.

Focal tumor irradiation, a cornerstone of cancer therapy, has been increasingly recognized for its capacity to provoke systemic immunogenic responses that extend beyond localized tumor control. Recent advances highlight DNA damage, especially DNA double-strand breaks (DSBs), as a central mediator linking radiotherapy to anti-tumor immune activation. Importantly, DNA misrepair, prevalent in cancer cells with deficient or dysregulated repair machinery, serves as a double-edged sword: while fostering tumor adaptation and genomic instability, it also fuels immune recognition through the accumulation of neoantigens, extracellular DNA release, immunogenic cell death, and the modulation of immune-related cytokines and chemokines. This review critically synthesizes the latest clinical and preclinical insights into the dynamic interplay between DNA damage, repair fidelity, and the immunogenic consequences of tumor irradiation. By focusing on the impact of DSB induction and misrepair processes, we underscore the emerging therapeutic opportunities of modulating DNA repair pathways during radiotherapy to potentiate anti-tumor immunity, particularly in synergy with immune checkpoint blockade. This article provides a comprehensive perspective on the molecular underpinnings and translational potential of harnessing irradiation-induced immunogenicity, offering a roadmap for future therapeutic strategies in radiation oncology and cancer immunotherapy. Not applicable

Genome instability is a central hallmark of cancer, driven by aberrant DNA damage responses that facilitate tumor evolution and resistance to therapy. Although canonical non‑homologous end joining and homologous recombination are well‑characterized pathways for repairing DNA double‑strand breaks (DSBs), recent advances have revealed that cancer cells increasingly depend on alternative end‑joining (alt‑EJ) to survive persistent DNA damage that arises from intrinsic stresses or external therapies. Alt‑EJ, characterized by its reliance on microhomologous sequences at DSB sites, promotes mutation accumulation and chromosomal rearrangements, thereby driving genomic instability and tumor progression. Despite its pivotal role in cancer biology, the molecular regulation, contextual determinants and dualistic role of alt‑EJ in maintaining genome integrity compared with promoting instability remain incompletely understood. The present review integrated the latest mechanistic insights into alt‑EJ, elucidated its regulatory networks and interactions with canonical DSB repair pathways and discussed its consequences for cancer genome integrity and evolution. Furthermore, it highlighted the emerging potential of alt‑EJ as a therapeutic vulnerability for cancer, underscoring the urgent need to translate these discoveries into innovative treatment strategies aimed at overcoming therapy resistance and improving patient outcomes.