Search Results (185)

Boron Neutron Capture Therapy (BNCT), as a promising oncological modality, enables the specific therapy of tumor cells while minimizing damage to healthy tissues. It has emerged as a critical strategy for combating refractory malignancies such as glioma, breast cancer, lung cancer, and hepatocellular carcinoma. The development of efficient boron carriers is fundamental to realizing the clinical potential of BNCT. This review systematically traces the evolutionary trajectory of boron carriers, from first-generation soluble borates and second-generation agents to third-generation actively targeted formulations, with a particular focus on the current state of nanoparticle-based carriers. It provides a detailed analysis of the structural properties, boron-loading advantages, targeting modification strategies, and key research findings associated with various nanoplatforms, including liposomes, polymers, dendrimers, boron carbide nanoparticles, and gold nanoparticles. Furthermore, by examining specific tumor cell targets such as folate receptors and integrin receptors, the review elucidates the mechanisms by which nanocarriers achieve tumor boron enrichment through both the enhanced permeability and retention (EPR) effect and ligand-mediated active targeting. The review also critically assesses current challenges in the field, including targeting efficacy, boron loading capacity, in vivo retention, and biocompatibility. Finally, it summarizes emerging strategies—such as multi-target modification, combination immunotherapy, theranostics, and the induction of tumor cell pyroptosis—and provides a forward-looking perspective on future developments, aiming to inform the rational design of next-generation BNCT boron carriers with high targeting specificity, high boron payload, and low toxicity. Full article

Purpose: To develop an accelerator neutron source suitable for boron neutron capture therapy—a new promising method for treating malignant tumors—and to develop dosimetry tools and methods. Methods: Research into the transport and acceleration of a beam of charged particles, development and manufacture of an accelerator neutron source, study of the radiation generated, and development and implementation of dosimetry tools and methods. Results: A facility called VITA has been created, which includes a tandem electrostatic accelerator of an original design for producing a 2.3 MeV 10 mA proton beam, a lithium target for generating neutrons in the ⁷Li(p,n)⁷Be reaction, and a beam shaping assembly for forming a therapeutic neutron beam. The facility at the institute is used for scientific research, the facility in Xiamen (China) is used for clinical trials, and the facility in Moscow (Russia) will soon be used for clinical trials. Also, new tools and methods for measuring the boron dose, γ-ray dose, and sum of the fast neutron dose and the nitrogen dose have been proposed and implemented. The conducted studies demonstrated the high efficiency of the VITA^® facility, the first possibility of implementing prompt γ-ray spectroscopy for boron imaging, and the first possibility of implementing lithium neutron capture therapy, which has advantages over BNCT, and also presented the results of the development of new tools and methods for measuring the boron dose, γ-ray dose, and the sum of the fast neutron dose and the nitrogen dose. Conclusions: The authors strongly recommend using prompt γ-ray spectroscopy in treatment and developing lithium neutron capture therapy, including in combination with BNCT, and note the high efficiency, reliability and compactness of the VITA^® facility. Full article

Background/Objectives: Boron neutron capture therapy (BNCT) relies on the selective delivery of boron-10 to tumor cells. Although 4-[¹⁰B]borono-L-phenylalanine (BPA) is currently the only clinically approved BNCT agent, it is limited by poor L-type amino acid transporter 1 (LAT1)/LAT2 selectivity and aqueous solubility. We previously developed 3-borono-5-fluoro-α-methyl-L-phenylalanine (5F-αMe-3BPA), a novel BPA derivative designed to be a LAT1-targeted BNCT/positron emission tomography theranostic agent. This study comprehensively characterizes its pharmacological profile and explores its pharmacokinetic optimization by modulating renal organic anion transporter 1 (OAT1). Methods: Transport kinetics of BPA, related analogs, and 5F-αMe-3BPA were analyzed in HEK293 cells stably expressing LAT1 or LAT2 using Michaelis–Menten analysis. Time-dependent cellular uptake and intracellular retention of BPA and 5F-αMe-3BPA were evaluated in T3M-4 pancreatic cancer cells with or without the LAT1 inhibitor JPH203. In vivo biodistribution was examined in T3M-4 tumor-bearing mice after intravenous administration of 5F-αMe-3BPA or BPA, with assessment of probenecid pretreatment. Results: 5F-αMe-3BPA retained LAT1 affinity comparable to that of BPA while showing markedly reduced LAT2-mediated transport, indicating improved LAT1/LAT2 selectivity. In T3M-4 cells, 5F-αMe-3BPA showed stronger LAT1 dependence, higher steady-state accumulation, and better intracellular retention than BPA under amino acid-containing conditions. Although 5F-αMe-3BPA achieved favorable tumor-to-plasma and tumor-to-muscle ratios in vivo, it was rapidly cleared from circulation. Probenecid pretreatment increased plasma exposure, reduced early renal accumulation, and significantly enhanced tumor boron accumulation, reaching approximately twofold higher levels than control. Conclusions: These findings establish 5F-αMe-3BPA as a highly LAT1-selective BNCT candidate and identify probenecid pretreatment as a clinically translatable pharmacokinetic strategy for maximizing therapeutic boron delivery. Full article

Background: Boron neutron capture therapy (BNCT) is a type of targeted radiotherapy with considerable therapeutic potential that may be combined with immune checkpoint inhibitors (ICIs) to enhance systemic antitumor immunity. Its efficacy relies on the efficient and safe delivery of boron to cancer cells. This study evaluated the acute toxicity of a self-assembling peptide-based boron carrier composed of A6K and sodium borocaptate (BSH) at a 1:10 molar ratio (A6K/BSH boron drug), which had previously shown excellent tumor-selective accumulation and prolonged intracellular retention. Methods: A single-dose intraperitoneal toxicity study was performed in 6-week-old BALB/c mice (n = 6 per group; 3 males and 3 females). Animals received BSH-equivalent doses of 0, 30, 100, 300, or 600 mg/kg and were observed for 14 days. Mortality, clinical signs, body weight, gross necropsy findings, and histopathological characteristics of major organs were then assessed. Results: No mortality or treatment-related clinical signs were observed. Body weight changes were comparable between the control and treated groups. Gross necropsy revealed no treatment-related abnormalities. Histopathology showed mild hepatocellular hypertrophy and granular degeneration without dose dependency. No other organ toxicities or sex-related differences were detected. Conclusions: A single intraperitoneal administration of the A6K/BSH boron drug up to 600 mg/kg (BSH-equivalent) produced no evident acute systemic toxicity, suggesting that the approximate lethal dose exceeds 600 mg/kg for both sexes. This initial safety assessment supports the further development of the A6K/BSH boron drug as a boron delivery agent for BNCT. Further studies are needed to confirm its safety under clinically relevant conditions. Full article

Boron neutron capture therapy (BNCT) is a binary targeted radiotherapy that uses boron agents to treat refractory malignancies. This study developed a novel boronophenylalanine (BPA)-loaded liposome doped with o-carborane (CB) for BNCT. We applied response surface methodology (RSM) to identify factors affecting BPA loading and optimized encapsulation efficiency (EE) to minimize BPA loss. In in vitro experiments, these liposomes demonstrated promising characteristics for BNCT. The nanoparticle properties of CB-BPA-Lips remain stable for at least 48 h, and CB-BPA-Lips can effectively reduce the release of the agents loaded within them. Both cell viability assays and apoptosis assays have shown that CB-BPA-Lips have good biocompatibility and a lower inhibitory effect on cell viability than BPA. Cellular boron uptake peaked at 47.3642 ng B/10⁶ cells in A549 lung cancer cells and peaked at 38.8875 ng B/10⁶ cells in Bronchial Epithelium transformed with Ad12-SV40 2B (BEAS-2B) human normal bronchial epithelial cells at 24 h post-treatment, with both exceeding uptake in the BPA control group. Overall, this work presents an optimized liposomal formulation that enhances boron delivery to cancer cells and provides a potential candidate boron agent for BNCT pending in-depth in vivo studies. Full article

Radiotherapy is one of the conventional methods for the treatment of cancers. Boron neutron capture therapy (BNCT) has emerged as a promising and well-recognized modality for treating certain types of cancers. BNCT is a binary radiotherapy that largely depends on neutron beams and ¹⁰B carriers. Although an “ideal” boron carrier should fulfill multiple criteria, high tumor/normal tissue ratio (T/N > 5) and high tumor uptake of boron (>20 μg/g) are critically important. First-generation (boric acid and derivatives) and second-generation (BPA and BSH) boron carriers suffer from poor T/N and extremely high dose in clinical use (500 mg/kg and usually >30 g for each patient). Glucose transporter 1 (GLUT1) is overexpressed on the membrane surface of multiple tumors and is a potential target for third-generation boron carrier to achieve high T/N and high tumor uptake of boron. However, the boron-bearing sugar derivatives designed in the last few decades have suffered from suboptimal T/N values and significant cytotoxicity. In the present study, a total of two categories comprising 6 series (28 in total) of boron-bearing sugar derivatives were designed and synthesized and their cellular boron uptake, T/N, and cytotoxicity were evaluated. The structure–activity relationship (SAR) of these target compounds was analyzed, and one of the target compounds, B3, a phenyl C-mannoside with an o-carborane moiety, exhibited the best boron-carrying profile, which featured 10.6-fold higher boron uptake by the SCC-9 cell line and a largely improved T/N (3.3 for B3 vs. 1.4 for BPA) compared with the current clinical gold standard BPA. Therefore, the chemical structure of B3 represents a privileged candidate structure for the future design of “ideal” boron carriers for BNCT. Full article

Boron neutron capture therapy (BNCT) is a biologically targeted, high–linear energy transfer radiotherapy that selectively delivers cytotoxic α-particles to boron-loaded tumor cells and has re-emerged with the development of hospital-compatible accelerator neutron sources and improved boron carriers. We performed a structured literature review of PubMed, Embase, and the Cochrane Library through October 2025 to summarize the radiobiological rationale, boron delivery strategies, and clinical outcomes of BNCT in glioblastoma (GBM) and other high-grade central nervous system tumors. Eligible clinical and translational studies were screened independently, and data on patient populations, boron agents, neutron source technologies, dosimetry, survival, response, and toxicity were extracted. Contemporary series and phase II trials indicate that BNCT is technically feasible and generally well tolerated, with encouraging survival outcomes in selected newly diagnosed and recurrent GBM, meaningful activity in recurrent high-grade meningiomas, and acceptable safety in limited pediatric cohorts. Current practice relies primarily on second-generation carriers such as boronophenylalanine and sodium borocaptate, while third-generation molecular and nanocarrier platforms remain in preclinical development. Overall, BNCT represents a promising high-LET, pharmacologically targeted modality for heavily pretreated and radioresistant CNS tumors, and ongoing prospective studies are needed to define its comparative effectiveness and optimal integration into patient care. Full article

Poly(amidoamine) (PAMAM) and poly-L-lysine (PLL) dendrimers have emerged as highly versatile macromolecular platforms with significant potential in biomedical applications, owing to their well-defined architecture, tunable surface chemistry, and capacity for multivalent functionalization. Their ability to carry substantial molecular payloads and to be engineered for selective interactions with biological systems has positioned them as attractive candidates for targeted drug delivery, including the transport of boron-rich compounds. Recent advances in dendrimer chemistry have enabled the incorporation of boron clusters into PAMAM and PLL structures, creating hybrid systems designed to enhance cellular uptake, improve tumor selectivity, and increase boron accumulation within malignant tissues. Given the growing interest in boron neutron capture therapy (BNCT), the integration of boron clusters into dendrimer structures represents a particularly promising direction for enhancing boron delivery to tumors. This manuscript reviews current knowledge on PAMAM and PLL dendrimers and their boron-functionalized derivatives, summarizing findings from cell culture studies, in vivo models, and clinical or preclinical investigations. Particular attention is given to both the advantageous properties of these dendrimers—such as improved delivery efficiency and biocompatibility—and their potential undesirable biological effects. As such, PAMAM and PLL dendrimers represent an important and evolving class of carriers that may significantly advance the effectiveness of boron neutron capture therapy (BNCT) in cancer treatment. Full article

Boron neutron capture therapy (BNCT) is a binary radiotherapy that is based on nuclear reactions between boron-10 and low-energy neutrons, which enables selective tumor cell killing. Although accelerator-based BNCT systems are increasingly being adopted, each platform requires independent biological validation. Here, we performed an in vitro preclinical evaluation of the linac-based iBNCT001 system employing a beryllium target in combination with the clinically approved boron drug SPM-011 (borofalan (¹⁰B)). Three complementary studies were conducted: (i) a cell-based BNCT efficacy study, (ii) a free-beam radiobiological evaluation, and (iii) a radiation leakage assessment using a human-phantom model. BNCT using iBNCT001 and SPM-011 induced clear boron concentration- and dose-dependent reductions in clonogenic survival across multiple tumor cell lines. Free-beam experiments determined a relative biological effectiveness (RBE) of 2.3 for the hydrogen dose component associated with high energy neutrons. In the phantom study, the maximum radiation leakage dose during head irradiation was 1.31 GyEq in the cervical region. Although this study is limited to in vitro biological assessments, the results provide non-clinical evidence supporting the efficacy, beam quality, and biological safety of iBNCT001 for future clinical BNCT applications. Full article

BNCT (Boron Neutron Capture Therapy) is a binary radiotherapeutic modality in which high LET (Linear Energy Transfer) particles are generated from ¹⁰B(n,α)⁷Li reaction, ideally within boron-loaded tumour cells, so the therapeutic outcome depends critically on the pharmacokinetics and biodistribution of boron carriers. In this review, boron-containing agents for BNCT, with a focus on ADMET (absorption, distribution, metabolism, excretion and toxicity) and model-informed design, were examined. Low-MW (low-molecular-weight) compounds, peptide conjugates, polymeric and nanostructured platforms and cell-based vectors were surveyed and how physicochemical properties, transporter engagement and nano–bio interactions govern tumour uptake, subcellular localisation and normal tissue exposure were discussed. A shift from maximising boron content towards optimising exposure profiles using PET (Positron Emission Tomography), PBK (physiologically based pharmacokinetic) modelling and in silico ADMET tools to define irradiation windows was also discussed. Classical agents such as BPA (Boronophenylalanine) and BSH (Sodium Borocaptate) are contrasted with newer polymeric and metallacarborane-based carriers, with attention to brain penetration, endosomal escape, linker stability, biodegradation and elimination routes, as well as platform-specific toxicities. Incontestably, further progress in BNCT will highly depend on integrating imaging-derived kinetics with PBPK-informed dose planning and engineering subcellularly precise yet degradable carriers, and that ADMET-guided design and spatiotemporal coordination are central to achieving reproducible clinical benefit from BNCT’s spatial selectivity. Full article

Boron neutron capture therapy (BNCT) is experiencing a global resurgence driven by advances in boron pharmacology, accelerator-based neutron sources, and molecular imaging-guided theranostics. BNCT produces high linear energy transfer particles with micrometer-range energy deposition, enabling cell-selective irradiation confined to boron-enriched tumor cells in a geometrically targeted region by the neutron beam. This mechanism offers the potential for exceptionally high therapeutic ratios, provided two core requirements are met: sufficient differential tumor uptake of ¹⁰B and a neutron beam with appropriate energy and penetration. After early clinical attempts in the mid-20th century were hindered by inadequate boron agents and reactor-based neutron beams, recent technological breakthroughs have made BNCT clinically viable. The development of hospital-compatible accelerator neutron sources, next-generation boron delivery systems (such as receptor-targeted compounds and nanoparticles), advanced theranostic approaches (such as ¹⁸F-BPA positron emission tomography and boron-sensitive magnetic resonance imaging), and AI-driven biodistribution modeling now support personalized treatment planning and patient selection. These innovations have catalyzed modern clinical implementation, exemplified by Japan’s regulatory approval of BNCT for recurrent head and neck cancer and the rapid expansion of clinical programs across Asia, Europe, and South America. Building on these foundations, BNCT has transitioned from a predominantly academic experimental modality into an increasingly commercialized and industrially supported therapeutic platform. The emergence of dedicated BNCT companies, international collaborations between accelerator manufacturers and hospitals, and pharmaceutical development pipelines for next-generation boron carriers has accelerated clinical translation. Moreover, BNCT now occupies a unique position among radiation modalities due to its hybrid nature, namely combining the biological targeting of radiopharmaceutical therapy with the external-beam controllability of radiotherapy, thereby offering new therapeutic opportunities where competitive approaches fall short. Emerging evidence suggests therapeutic promise in glioblastoma, recurrent head and neck cancers, melanoma, meningioma, lung cancer, sarcomas, and other difficult-to-treat malignancies. Looking ahead, continued innovation in compact neutron source engineering, boron nanocarriers, multimodal theranostics, microdosimetry-guided treatment planning, and combination strategies with systemic therapies such as immunotherapy will be essential for optimizing outcomes. Together, these converging developments position BNCT as a biologically targeted and potentially transformative modality in the era of precision oncology. Full article

Background: Boron neutron capture therapy (BNCT) represents a highly selective therapeutic modality for recalcitrant cancers, leveraging the nuclear reaction initiated by thermal neutron capture in boron-10 (¹⁰B) to deliver high-linear energy transfer radiation (α-particles and ⁷Li ions) directly within tumor cell boundaries. However, the widespread clinical adoption of BNCT is critically hampered by the pharmacological challenge of achieving sufficiently high, tumor-selective intracellular ¹⁰B concentrations (20–50 μg of ¹⁰B/g tissue). Conventional small-molecule boron carriers often exhibit dose-limiting non-specificity, rapid systemic clearance, and poor cellular uptake kinetics. Methods: To overcome these delivery barriers, we synthesized and characterized a novel dual-modality nanoplatform based on highly biocompatible, functionalized graphene oxide (GO). This platform was structurally optimized via covalent conjugation with high-boron content carborane clusters (dodecacarborane derivatives) for enhanced BNCT efficacy. Crucially, the nanocarrier was further decorated with plasmonic gold nanostructures (AuNPs), endowing the system with intrinsic surface-enhanced Raman scattering (SERS) properties, enabling real-time, high-resolution intracellular tracking and quantification. Results: We evaluated the synthesized GO@Carborane@Au nanoplatforms for their stability, cytotoxicity, and internalization characteristics. Cytotoxicity assays demonstrated excellent biocompatibility against the non-malignant human keratinocyte line (HaCaT) while showing selective toxicity (upon irradiation, if tested) and high cellular uptake efficiency in the aggressive human glioblastoma tumor cell line (T98G). The integrated plasmonic component allowed for the successful, non-destructive monitoring of nanoplatform delivery and accumulation within both HaCaT and T98G cells using SERS microscopy, confirming the potential for pharmacokinetic and biodistribution studies in vivo. Conclusions: This work details the successful synthesis and preliminary in vitro validation of a unique graphene oxide-based dual-modality nanoplatform designed to address the critical delivery and monitoring challenges of BNCT. By combining highly efficient carborane delivery with an integrated photonic trace marker, this system establishes a robust paradigm for next-generation theranostic agents, significantly advancing the potential for precision, image-guided BNCT for difficult-to-treat cancers like glioblastoma. Full article

Boron Neutron Capture Therapy (BNCT) is a radiotherapeutic modality which couples selective pharmacological delivery of ¹⁰B with irradiation by low-energy neutrons to achieve highly localized tumor cell killing. The BNCT therapeutic approach is undergoing rapid evolution driven primarily by advances in compact accelerator-driven neutron-source and associated facility-level nuclear infrastructure. This review examines the key physical and radiobiological principles of BNCT, with emphasis on the current engineering and operational aspects, such as neutron production and moderation, spectral shaping, beam optimization and dosimetric quantification, that critically influence clinical translation. Recent progress in ¹⁰B production and enrichment, as well as in strategies for efficient ¹⁰B delivery, is also briefly addressed. By tracing the pathway from neutron source to clinical target, this review defines the state of the art in BNCT technology, identifies the main physical and infrastructural challenges, and delineates the multidisciplinary advances needed to support widespread clinical implementation of next-generation BNCT systems. Full article

Boron is a trace element with multifaceted chemical and biological properties that underpin its emerging relevance in human health and medicinal chemistry. Although present in organisms at very low concentrations, boron participates in key physiological processes, including mineral metabolism, bone homeostasis, hormonal regulation, immune modulation, and redox balance. Its unique electronic structure—characterized by electron deficiency and the ability to form multi-center bonds—gives rise to diverse allotropic, cluster, and coordination chemistries, enabling the formation of biologically active complexes and therapeutic agents. Dietary boron, derived mainly from plant-based foods, is efficiently absorbed and predominantly excreted by the kidneys, showing a strong correlation between intake and urinary levels. Current evidence suggests beneficial effects of boron on bone mineral density, cognitive function, inflammation, antioxidant defenses, and metabolic regulation, although the precise molecular mechanisms remain partially understood. In medicinal chemistry, a broad spectrum of boron-containing compounds—including borates, boronic acids, boronated amino acids, carboranes, and metallacarboranes—has gained clinical and preclinical importance. These compounds serve as enzyme inhibitors, antimicrobial and anti-inflammatory agents, metabolic modulators, and critical boron carriers in boron neutron capture therapy (BNCT), which leverages the neutron-capture properties of ¹⁰B for targeted cancer treatment. Advances in synthesis, functionalization, and nanocarrier design have expanded the therapeutic potential of boron-based molecules. Ongoing research aims to optimize their selectivity, biodistribution, safety, and diagnostic integration. Overall, boron represents a versatile and rapidly developing component of modern biomedical science, with promising implications for oncology, infectious diseases, metabolic disorders, and precision medicine. Full article

Background: The synthesis and biological investigation of pyrrolidine (L-gulo) iminosugars bearing an organic boron pharmacophore in ortho and meta positions of an N-benzyl group is reported. This paper completes the structure–activity relationship data for this novel family of boron-bearing iminosugars. These can establish reversible intramolecular interactions via dative bonding from nucleophilic amino acid side chains to the empty p-orbital of the boron atom. Methods: Inhibitory activities against two panels of glycosidases and cancer cell lines were investigated to ascertain structure–activity relationship profiles for these novel iminosugar drug leads. Results: These iminosugars display selective, moderate-to-weak inhibitions (IC₅₀s = 116–617 μM) of β-D-galactosidase (bovine liver), and indications of inhibition of β-D-glucosidases (almond, bovine liver) (IC₅₀s = 633 and 710 μM) and α-D-glucosidases (rice, yeast, rat intestinal maltase) (IC₅₀s = 106–784 μM). The boronic acid group emerges as a useful pharmacophore for management of lysosomal storage disorders via the chaperone-mediated therapy approach. The cancer assays revealed that the A2780 ovarian carcinoma cell line is selectively inhibited by all compounds screened and the MIA-Pa-Ca2 pancreatic carcinoma cell line is selectively inhibited by most compounds. Growth inhibition and GI₅₀ values were most potent for the meta 7 side-product. Conclusions: Beyond the cancer cell line inhibition and dose-response capabilities, the real therapeutic potential of these borylated drugs lies in their switch on/switch off activation under boron neutron capture therapy (BNCT) radiotherapeutic conditions, thus providing an important area of application for borylated monosaccharides. Full article