Search Results (201)

One of the promising research areas involving carborane derivatives is boron neutron capture therapy (BNCT). Due to the high boron atom content in carborane molecules, these compounds are considered potential candidates for BNCT-based cancer treatment. Despite ongoing studies on various biologically active carboranyl-containing compounds, the search continues for substances that meet the stringent requirements of effective BNCT agents. In this study, the synthesis of carboranyl-containing derivatives of β-arylaliphatic acids is described, along with the investigation of their reactivity with primary and secondary amines, as well as with metals and their hydroxides. The molecular structures of the synthesized compounds were confirmed using Fourier-transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, elemental analysis, and mass spectrometry (LC-MS). Cytotoxicity of the water-soluble compound potassium 3-(2-isopropyl-1,2-dicarba-closo-dodecaboran-1-yl)-3-phenylpropanoate was evaluated using several cell lines, including HdFn and MCF-7. Full article

Heat-stable enterotoxin (STa) is a peptide toxin that induces acute diarrhea by binding to guanylyl cyclase C (GC-C) in intestinal epithelial cells. Interestingly, GC-C is highly expressed not only in intestinal cells but also in certain colorectal cancer cells, such as T84 and Caco-2 cells. This unique expression pattern provides STa as an effective candidate for therapeutic applications in cancer suppression or as a probe for detecting cancer cells. Recently, we developed attenuated forms of several STa analogs, including STa topological isomers, and evaluated their efficacy in detecting GC-C on Caco-2 cells, which enables the use of STa in human applications. Therefore, in this study, we investigated the potential application of a ¹⁰B-labeled STa derivative, [Mpr⁵,D-Lys¹⁶(BSH)]-STp(5–17) topological isomer, in boron neutron capture therapy (BNCT), for establishing a novel therapeutic strategy for colorectal cancer. The ¹⁰B-labeled STa peptide clearly exhibited Caco-2 cell killing activity upon neutron irradiation in a concentration-dependent manner, indicating that STa is an effective candidate drug for BNCT. To our knowledge, this is the first report of using STa in boron neutron capture therapy (BNCT). Full article

Background: Boron Neutron Capture Therapy (BNCT) is a promising cancer treatment that combines tumor-selective boron delivery agents with thermal neutrons to kill cancer cells while sparing normal tissue. BNCT requires boron-containing compounds that exhibit high tumor selectivity and achieve therapeutic boron concentrations within tumor cells. This work focuses on the early development of a novel boron cluster carbohydrate derivative based on the glucosamine structure. Our results indicate that this derivative may have advantages over the typical boron delivery agent used in clinical applications and may significantly improve boron delivery capacity at the cellular level. Methods: The performance of the compound in terms of boron uptake was tested in the U87-MG glioblastoma cell line employing neutron autoradiography imaging and quantification. Results: The compound was non-toxic for cells, and it showed a remarkable capacity to enrich cells with boron. The ratio between boron concentration provided in the culture medium and boron concentration achieved in cells was compared to that obtained with boronophenylalanine (BPA), the gold standard in BNCT. The result demonstrated a significantly better performance compared with BPA, showing that the novel agent can concentrate boron in cells more than in culture medium. Conclusions: The encouraging preliminary results provide a starting point for its potential application in in vivo tests. Full article

Recently, studies on accelerator-based boron neutron capture therapy (AB-BNCT) systems for cancer treatment have attracted the attention of researchers around the world. A neutron source can be obtained through the impingement of high-intensity proton beams emitted from the accelerator onto the target. This process would deposit a large amount of heat within this target. A thermal management system design is needed for AB-BNCT systems to prevent the degradation of the target due to thermal/mechanical loading. However, there are few studies that investigate this topic. In this paper, a cooling channel with a boiling heat transfer mechanism is numerically designed for thermal management in order to remove heat deposited in the Be target of the AB-BNCT system of Heron Neutron Medical Corp. A three-dimensional (3D) CFD methodology with a two-fluid model and an RPI wall boiling model is developed to investigate its availability. Two subcooled boiling experiments from previous works are adopted to validate the present CFD boiling model. This validated model can be confidently applied to assist in thermal management design for the AB-BNCT system. Based on the simulation results under the typical operating conditions of the AB-BNCT system set by Heron Neutron Medical Corp., the present coolant channel employing the boiling heat transfer mechanism can efficiently remove the heat deposited in the Be target, as well as maintain its integrity during long-term operation. In addition, compared with the channel with the single-phase convection traditionally designed for an AB-BNCT system, the boiling heat transfer mechanism can result in a lower peak temperature in the Be target and its corresponding deformation. Full article

Radiotherapy (RT) has undergone transformative advancements since its inception over a century ago. This review highlights the most promising and impactful innovations shaping the current and future landscape of RT. Key technological advances include adaptive radiotherapy (ART), which tailors treatment to daily anatomical changes using integrated imaging and artificial intelligence (AI), and advanced image guidance systems, such as MR-LINACs, PET-LINACs, and surface-guided radiotherapy (SGRT), which enhance targeting precision and minimize collateral damage. AI and data science further support RT through automation, improved segmentation, dose prediction, and treatment planning. Emerging biological and targeted therapies, including boron neutron capture therapy (BNCT), radioimmunotherapy, and theranostics, represent the convergence of molecular targeting and radiotherapy, offering personalized treatment strategies. Particle therapies, notably proton and heavy ion RT, exploit the Bragg peak for precise tumor targeting while reducing normal tissue exposure. FLASH RT, delivering ultra-high dose rates, demonstrates promise in sparing normal tissue while maintaining tumor control, though clinical validation is ongoing. Spatially fractionated RT (SFRT), stereotactic techniques and brachytherapy are evolving to treat challenging tumor types with enhanced conformality and efficacy. Innovations such as 3D printing, Auger therapy, and hyperthermia are also contributing to individualized and site-specific solutions. Across these modalities, the integration of imaging, AI, and novel physics and biology-driven approaches is redefining the possibilities of cancer treatment. This review underscores the multidisciplinary and translational nature of modern RT, where physics, engineering, biology, and informatics intersect to improve patient outcomes. While many approaches are in various stages of clinical adoption and investigation, their collective impact promises to redefine the therapeutic boundaries of radiation oncology in the coming decade. Full article

Background/Objectives: Boron neutron capture therapy (BNCT) is a promising, less-invasive anticancer treatment. However, the development of effective boron-based agents (BNCT probes) remains a critical and challenging issue. Previously, we developed a styrene–maleic acid (SMA) copolymer conjugated with glucosamine, encapsulating boronic acid, which exhibited tumor-targeted distribution via the enhanced permeability and retention (EPR) effect. Building upon this approach, in this study, we designed and synthesized a series of SMA-based polymeric probes for BNCT and evaluated their biological activities, with a particular focus on tumor-targeting properties. Methods: Two SMA-based BNCT nanoprobes, SMA–glucosamine conjugated Borax (SG@B) and SMA-conjugated aminophenylboronic acid encapsulating tavaborole (S-APB@TB), were designed and synthesized. The boron content in the conjugates was quantified using inductively coupled plasma mass spectrometry (ICP-MS), while particle sizes were measured via dynamic light scattering (DLS). In vitro cytotoxicity was assessed using the MTT assay in mouse colon cancer C26 cells. The tissue distribution of the conjugates was analyzed in a mouse sarcoma S180 solid tumor model using ICP-MS. Results: Both SG@B and S-APB@TB formed nanoformulations with average particle sizes of 137 nm and 99 nm, respectively. The boron content of SG@B was 2%, whereas S-APB@TB exhibited a significantly higher boron content of 14.4%. Both conjugates demonstrated dose-dependent cytotoxicity against C26 cells, even in the absence of neutron irradiation. Notably, tissue distribution analysis following intravenous injection revealed higher boron concentrations in plasma and tumor tissues compared to most normal tissues, with S-APB@TB showing particularly favorable tumor accumulation. Conclusions: These findings highlight the tumor-targeting potential of SMA-based BNCT nanoprobes. Further investigations are warranted to advance their clinical development as BNCT agents. Full article

Boron Neutron Capture Therapy is a re-emerging therapy for the treatment of cancer, and the development of new neutron-reactive nuclei carriers with enhanced efficiency is of great importance. In this work we propose three new boron-based solid compounds, of formulas [Ca(H₂O)₆](C₁₄H₈O₆B)₂ (CaSB), [Cu(C₁₄H₈O₆B)] (CuSB), and [Li(C₁₄H₈O₆B)(H₂O)] (LiSB), usable as nanoparticles for the carriage of the ¹⁰B isotope. The copper atom in CuSB was introduced because it is known that its presence magnifies the effect of the radiation on cells. Furthermore, the lithium atom in LiSB also allows us to include the ⁶Li isotope, which can take part in the nuclear reactions, enhancing the efficiency of the anti-cancer treatment. The compounds were characterized with single-crystal X-ray diffraction to compare the densities of the reactive isotopes in the materials, a key parameter related to the efficiency of the materials. In this work, we used a computational method to calculate the dose absorbed by a tumor mass treated with nanoparticles of the compounds in order to select the most efficient one for the therapy. The results reported in this work are encouraging. Full article

Boron neutron capture therapy (BNCT) is a specialized cancer treatment that leverages the high absorption cross-section of boron for thermal neutrons. When boron captures neutrons, it undergoes a nuclear reaction that produces alpha particles and lithium ions, which have high linear energy transfer (LET) and can effectively damage nearby cancer cells while minimizing harm to surrounding healthy tissues. This targeted approach makes BNCT particularly advantageous for treating tumors situated in sensitive areas where traditional radiation therapies may pose risks to critical structures. In this study, the deuterium–deuterium (DD) neutron generator, specifically the DD-110 model (neutron yield Y = 1 × 10¹⁰ n/s), served as the neutron source for BNCT. The fast neutrons produced by this generator were thermalized to the epithermal energy range using a beam-shaping assembly (BSA). The BSA was designed with a moderator composed of 32 cm of MgF₂, a reflector made of 76 cm of Pb, and filters including 3 cm of Pb and 1.52 cm of Bi. A collimator, featuring a 10 cm high Pb cone frustum with a 12 cm aperture diameter, was also employed to optimize beam characteristics. The entire system’s performance was modeled and simulated using the MCNPX code, focusing on parameters both in-air and in-phantom to evaluate its efficacy. The findings indicated that the BSA configuration yielded an optimal thermal-to-epithermal flux ratio (${\phi }_{ther}$/${\phi }_{epth}$) of 0.19, a current-to-flux ratio of 0.87, and a gamma dose-to-epithermal flux ratio of 1.71 × 10⁻¹³ Gy/cm², all aligning with IAEA recommendations. The simulated system showed acceptable ratios for ${\phi }_{ther}$/${\phi }_{epth}$, gamma dose to epithermal flux, and beam collimation. Notably, the advantage depth was recorded at 5.5 cm, with an advantage ratio of 2.29 and an advantage depth dose rate of 4.1 × 10⁻⁴ Gy.Eq/min. The epithermal neutron flux of D110 exceeded D109, but D110’s fast neutron contamination increased ~6.6 times. On the other hand, D110’s gamma contamination decreased by 30%. Based on these findings, optimizing neutron source characteristics is crucial for BNCT efficacy. Future research should focus on developing advanced neutron generators that balance these factors, aiming to produce optimal neutron yields for enhanced treatment outcomes and broader applicability. Full article

BODIPY (Boron-Dipyrromethene) dyes have emerged as versatile fluorescent probes in cellular imaging and therapeutic applications owing to their unique chemical properties, including high fluorescence quantum yield, strong extinction coefficients, and remarkable photostability. This review synthesizes the recent advancements in BODIPY dyes, focusing on their deployment in biological imaging and therapy. The exceptional ability of BODIPY dyes to selectively stain cellular structures enables precise visualization of lipids, proteins, and nucleic acids within live and tumor cells, thereby facilitating enhanced understanding of biochemical processes. Moreover, BODIPY derivatives are increasingly utilized in Photodynamic therapy (PDT) and Photothermal therapies (PTT) for targeting cancer cells, where their capability to generate cytotoxic reactive oxygen species upon light activation offers a promising approach to tumor treatment. Recently, BODIPY derivatives have been used for Boron Neutron Capture Therapy (BNCT) for various tumors, and it is a growing research field. Advancements in nanotechnology have allowed the fabrication of BODIPY dye-based nanomedicines, either alone or with the use of metallic nanoparticles as a matrix offering the development of a new class of bioimaging and theragnostic agents. This review also discusses innovative BODIPY-based formulations and strategies that amplify therapeutic efficacy while minimizing adverse effects, underscoring the potential of these dyes as integral components in next-generation diagnostic and therapeutic modalities. By summarizing current research and future perspectives, this review highlights the critical importance of BODIPY dyes in advancing the fields of cellular imaging and treatment methodologies. Full article

Background/Objectives: Boron neutron capture therapy (BNCT) is a promising approach for selectively targeting and destroying malignant cells using ¹⁰B isotopes. A significant challenge in BNCT lies in the development of efficient boron delivery systems that ensure adequate boron accumulation within tumor cells. This study aims to synthesize, characterize, and evaluate COSAN-functionalized nanoparticles (NP@I-COSAN) as a potential boron carrier for BNCT. Methods: Hybrid nanoparticles were synthesized by conjugating monoiodinated cobaltabisdicarbollides (I-COSAN) to commercially available acrylic polymer-based nanoparticles. Functionalization and cellular uptake were confirmed through FTIR, TGA, UV-Vis spectroscopy, and TEM/EDX analyses. Biocompatibility was evaluated by assessing cytotoxicity in HeLa cells and C. elegans as an in vivo model. Intracellular boron uptake was quantified using ICP-MS, with results compared to those obtained with 4-borono-L-phenylalanine conjugated to fructose (f-BPA). An in vitro BNCT proof-of-concept assay was also performed to evaluate therapeutic efficacy. Results: NP@I-COSAN demonstrated low cytotoxicity and efficient internalization in cells. ICP-MS analysis revealed stable boron retention, comparable to traditional boron agents. The BNCT assay further showed that NP@I-COSAN was effective in inducing tumor cell apoptosis, even at lower boron concentrations than conventional treatments. Conclusions: These results underscore the potential of NP@I-COSAN as an effective boron delivery system for BNCT, offering a promising strategy to enhance boron accumulation within tumor cells and improve treatment efficacy. Full article

Background/Objectives: Cancer-associated fibroblasts (CAFs), which are an important component of the tumor microenvironment, have been reported to have an adverse effect on conventional radiotherapy. This study aims to elucidate the effects of CAFs in boron neutron capture therapy (BNCT) using a three-dimensional (3D) oral cancer model. Methods: Three-dimensional cancer models were fabricated using patient-derived CAFs or patient-derived normal oral fibroblasts (NOFs) and a human oral squamous cell carcinoma cell line. Each 3D cancer model was performed with either a conventional X-ray treatment or BNCT and additionally analyzed histomorphologically. Results: The 3D oral cancer-CAFs model demonstrated a greater depth of cancer cell invasion than the 3D oral cancer-NOFs model. Radiation therapy for the 3D oral cancer models indicated a trend for decreasing cancer cell invasion and cell number with dose dependence in both X-ray and BNCT. In comparison with X-rays, BNCT showed a consistent increase in the number of NOFs and a significant reduction in the number of CAFs. Conclusions: BNCT for the 3D oral cancer model was shown to be effective against cancer cells and CAFs but not against NOFs, indicating its usefulness as a minimally invasive treatment for advanced cancer. Furthermore, it is indicated that the 3D oral cancer-CAFs model is a valuable tool to evaluate cancer treatment and research, particularly in high-grade malignant tumors with invasion. Full article

Boron Neutron Capture Therapy (BNCT) is a therapeutic approach used to treat malignancies that are difficult to localise and typically inoperable. This therapy involves two stages: the administration of the boron (¹⁰B) isotope, which selectively enters cancer cells without affecting healthy tissue, followed by irradiation of the tumour with a neutron beam. In this study, boron carbide (B₄C), a ceramic material with exceptional physical and chemical properties, was used as a nanoparticle platform for BNCT. The surface of the boron carbide nanoparticles was optimised by modifying them with compounds such as dextrin, dextran T70, sorbitol, lysine, and arginine. Boron carbide was synthesised directly from boron and carbon and then subjected to grinding, washing, and centrifugation. The unmodified and modified samples were analysed for their particle size, zeta potential, and toxicity against glioblastoma T98G cells. Additionally, FTIR spectroscopy confirmed the successful surface modifications. The results demonstrate that boron carbide, as a ceramic material, can be effectively functionalised with biocompatible compounds. Among the tested modifications, B₄C-dextrin and B₄C-dextran T70 exhibited the highest toxicity towards cancer cells, demonstrating the potential of ceramic platforms in biomedical applications. Full article

Melanoma is an aggressive disease that arises from mutations in the cells that produce the pigment melanin, melanocytes. Melanoma is characterized by a high mortality rate, due to avoidance of applied therapies and metastasis to other organs. The peculiar features of boron neutron capture therapy (BNCT), particularly its cell-level selectivity, make BNCT a promising modality for melanoma treatment. However, appropriate cellular models should be used to study new therapies or improve the efficacy of existing therapies. Spheroids, which have been used for years for in vitro studies of the efficacy of anti-cancer therapies, have many characteristics shared with tumors through which they can increase the accuracy of the cellular response compared to 2D culture in vitro studies and reduce the use of animals for research in the future. To the best of our knowledge, when we started researching the use of spheroids in BNCT in vitro, there was no publication showing such use. Our study aimed to evaluate the efficacy of a 3D cellular model (spheroids) for testing BNCT on melanoma cells. We assessed boronophenylalanine (¹⁰BPA) uptake using inductively coupled plasma mass spectrometry in both spheroids and 2D cultures of melanoma and melanocytes. DNA damage, Ki67 protein expression, and spheroid growth were analyzed. The experimental groups included: (1) IR_B (neutron flux + 50 µg ¹⁰B/mL), (2) IR (neutron flux alone), (3) C_B (no irradiation, 50 µg ¹⁰B/mL), and (4) C (no irradiation and no treatment with boron). The total absorbed doses were estimated to be 2.1–3.1 Gy for IR_B cells and spheroids as well as 8.3–9.4 Gy for IR_B spheroids, while estimated doses for IR cells were 0.5–1.9 Gy. The results indicated that IR_B spheroids might exhibit a reduced diameter. Melanoma cells in the 3D model showed that their DNA damage levels may be higher than those in the 2D model. Moreover, the Ki67 assay revealed differences in the expression of this marker between irradiated melanoma cell lines. In conclusion, preincubation with ¹⁰BPA enhances BNCT efficacy, leading to cell growth inhibition and increased DNA fragmentation. Differences in DNA damage between 2D and 3D models may be due to dissimilarities in cell metabolism caused by a changed cell architecture. Full article

Boron Neutron-Capture Therapy (BNCT) is a form of radiation therapy that relies on the highly localized and enhanced biological effects of the ¹⁰B neutron capture (BNC) reaction products to selectively kill cancer cells. The efficacy of BNCT is, therefore, strongly dependent on the ¹⁰B spatial microdistribution at a subcellular level. Fluorescent Nuclear Track Detectors (FNTDs) could be a promising technology for measuring ¹⁰B microdistribution. They allow the measurement of the tracks of charged particles, and their biocompatibility allows cell samples to be deposited and grown on their surfaces. If a layer of borated cells is deposited and irradiated by a neutron field, the energy deposited by the BNC products and their trajectories can be measured by analyzing the corresponding tracks. This allows the reconstruction of the position where the measured particles were generated, hence the microdistribution of ¹⁰B. With respect to other techniques developed to measure ¹⁰B microdistribution, FNTDs would be a non-destructive, biocompatible, relatively easy-to-use, and accessible method, allowing the simultaneous measurement of the ¹⁰B microdistribution, the LET of particles, and the evolution of the related biological response on the very same cell sample. An FNTD was tested in three irradiation conditions to study the feasibility of FNTDs for BNCT applications. The FNTD allowed the successful measurement of the correct alpha particle range and mean penetration depth expected for all the radiation fields employed. This work proved the feasibility of FNTD in reconstructing the tracks of the alpha particles produced in typical BNCT conditions, thus the ¹⁰B microdistribution. Further experiments are planned at the University of Pavia’s LENA (Applied Nuclear Energy Laboratory) to test the final set-up coupling the FNTD with borated cell samples. Full article

Brain diseases pose significant treatment challenges due to the restrictive nature of the blood–brain barrier (BBB). Recent advances in targeting macromolecules offer promising avenues for overcoming these obstacles through receptor-mediated transcytosis (RMT). We summarize the current progress in targeting brain drug delivery with macromolecules for brain diseases. This exploration details the transport mechanisms across the BBB, focusing on RMT and its use of natural ligands for drug delivery. Furthermore, the review examines macromolecular ligands such as antibodies, peptides, and aptamers that leverage RMT for effective BBB traversal. Advancements in macromolecules-based delivery systems for brain diseases are summarized, emphasizing their therapeutic potential and limitations. Finally, emerging RMT strategies, including viral vectors, exosomes, and boron neutron capture therapy, are discussed for their precision in brain-targeted treatments. This comprehensive overview underscores the potential of RMT-based approaches to revolutionize brain disease therapy. Full article