In vivo evaluation of the effects of combined boron and gadolinium neutron capture therapy in mouse models

Lee, Woonghee; Kim, Kyung Won; Lim, Jinhyuk; Sarkar, Swarbhanu; Kim, Jung Young; Chang, Yongmin; Yoo, Jeongsoo

doi:10.1038/s41598-022-17610-4

Cited by 7 publications

(5 citation statements)

References 22 publications

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“…Combining boron and gadolinium in the same formulation requires the evaluation of possible synergistic effects that could, in turn, demand further optimization of the ratio between 10 B and 157 Gd . The presence of Gd could cause a shielding effect and thus reduce the effectiveness of neutron irradiation [ 31 ]. Moreover, dosimetry in the presence of Gd is particularly challenging due to the broad spectrum of secondary radiation and the biological effect linked to the capacity of Gd to reach the cell nucleus.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and Characterization of Gd-Functionalized B4C Nanoparticles for BNCT Applications

Vitali

Demichelis

Martino

et al. 2023

Life

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Inorganic nanoparticles of boron-rich compounds represent an attractive alternative to boron-containing molecules, such as boronophenylalanine or boranes, for BNCT applications. This work describes the synthesis and biological activity of multifunctional boron carbide nanoparticles stabilized with polyacrylic acid (PAA) and a gadolinium (Gd)-rich solid phase. A fluorophore (DiI) was included in the PAA functionalization, allowing the confocal microscopy imaging of the nanoparticles. Analysis of the interaction and activity of these fluorescent Gd-containing B4C nanoparticles (FGdBNPs) with cultured cells was appraised using an innovative correlative microscopy approach combining intracellular neutron autoradiography, confocal, and SEM imaging. This new approach allows visualizing the cells, the FGdBNP, and the events deriving from the nuclear process in the same image. Quantification of 10B by neutron autoradiography in cells treated with FGdBNPs confirmed a significant accumulation of NPs with low levels of cellular toxicity. These results suggest that these NPs might represent a valuable tool for achieving a high boron concentration in tumoral cells.

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Section: Discussionmentioning

confidence: 99%

Synthesis and Characterization of Gd-Functionalized B4C Nanoparticles for BNCT Applications

Vitali

Demichelis

Martino

et al. 2023

Life

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“…Because the injection dose of Gd-MID-BSA in irradiation experiments was half the dose of the MRI and biodistribution experiments, the gadolinium concentration in the tumor could be lower than 100 μg[Gd]/g, resulting in an additive therapeutic effect rather than a shielding effect. In previous studies, the boron source and gadolinium source were highly concentrated in liposomes at tens of millimolar and administrated into animals separately . It means that there were scattered regions with high boron and gadolinium concentrations locally in tumor tissues, while the apparent concentrations were calculated as average.…”

Section: Results and Discussionmentioning

confidence: 99%

“…While we observed improvements in the therapeutic efficacy with Gd-MID-BSA, several studies have reported a decrease in the effectiveness of BNCT when gadolinium concentrations exceed 100 μg/g. 37,48 These decreases could be attributed to the shielding effect caused by gadolinium, which possesses a large neutron cross section. Because the injection dose of Gd-MID-BSA in irradiation experiments was half the dose of the MRI and biodistribution experiments, the gadolinium concentration in the tumor could be lower than 100 μg[Gd]/g, resulting in an additive therapeutic effect rather than a shielding effect.…”

Section: Synthesis Of Maleimide Do3a (3)mentioning

confidence: 99%

“…In previous studies, the boron source and gadolinium source were highly concentrated in liposomes at tens of millimolar and administrated into animals separately. 48 It means that there were scattered regions with high boron and gadolinium concentrations locally in tumor tissues, while the apparent concentrations were calculated as average. On the other hand, in this study, we bound both boron and gadolinium to the same albumin molecule that contributed to the homogeneous distribution of boron and gadolinium in the tissues.…”

Section: Synthesis Of Maleimide Do3a (3)mentioning

confidence: 99%

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Development of a Gadolinium–Boron-Conjugated Albumin for MRI-Guided Neutron Capture Therapy

Okada,

Nishimura,

Ainaya

et al. 2023

Mol. Pharmaceutics

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Noninvasive monitoring of boron agent biodistribution is required in advance of neutron capture therapy. In this study, we developed a gadolinium–boron-conjugated albumin (Gd-MID-BSA) for MRI-guided neutron capture therapy. Gd-MID-BSA was prepared by labeling bovine serum albumin with a maleimide-functionalized gadolinium complex and a maleimide-functionalized closo-dodecaborate orthogonally. The accumulation of Gd-MID-BSA in tumors in CT26 tumor-bearing mice reached a maximum at 24 h after the injection, as confirmed by T 1-based MRI and biodistribution analysis using inductively coupled plasma optical emission spectrometry. The concentrations of boron and gadolinium in the tumors exceeded the thresholds required for boron neutron capture therapy (BNCT) and gadolinium neutron capture therapy (GdNCT), respectively. The boron concentration ratios of tumor to blood and tumor to normal tissues satisfied the clinical criteria, indicating the reduction of undesired nuclear reactions of endogenous nuclei. The molar ratio of boron to gadolinium in the tumor was close to that of Gd-MID-BSA, demonstrating that the accumulation of Gd-MID-BSA in the tumor can be evaluated by MRI. Thermal neutron irradiation with Gd-MID-BSA resulted in significant suppression of tumor growth compared to the group injected with a boron-conjugated albumin without gadolinium (MID-BSA). The neutron irradiation with Gd-MID-BSA did not cause apparent side effects. These results demonstrate that the conjugation of gadolinium and boron within the albumin molecule offers a novel strategy for enhancing the therapeutic effect of BNCT and the potential of MRI-guided neutron capture therapy as a promising treatment for malignant tumors.

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“…These data highlight the promising potential of combining ACG gel with PD-1 blockade to prevent postoperative tumor recurrence and improve survival rates. Therefore, in contrast to other tumor therapies that also require exogenous irradiation, such as boron neutron capture therapy (BNCT) and gadolinium neutron capture therapy (GdNCT), PDT, and photothermal therapy (PTT), our approach offers the unique benefit of directly reshaping TME in addition to killing tumor cells, which enables the immune system to eradicate residual tumors and prevent tumor recurrence. − …”

mentioning

confidence: 99%

In Situ Formed Microalgae-Integrated Living Hydrogel for Enhanced Tumor Starvation Therapy and Immunotherapy through Photosynthetic Oxygenation

Zhang,

Han,

Chen

et al. 2024

Nano Lett.

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The effectiveness of various cancer therapies for solid tumors is substantially limited by the highly hypoxic tumor microenvironment (TME). Here, a microalgae-integrated living hydrogel (ACG gel) is developed to concurrently enhance hypoxia-constrained tumor starvation therapy and immunotherapy. The ACG gel is formed in situ following intratumoral injection of a biohybrid fluid composed of alginate, Chlorella sorokiniana, and glucose oxidase, facilitated by the crossing-linking between divalent ions within tumors and alginate. The microalgae Chlorella sorokiniana embedded in ACG gel generate abundant oxygen through photosynthesis, enhancing glucose oxidase-catalyzed glucose consumption and shifting the TME from immunosuppressive to immunopermissive status, thus reducing the tumor cell energy supply and boosting antitumor immunity. In murine 4T1 tumor models, the ACG gel significantly suppresses tumor growth and effectively prevents postoperative tumor recurrence. This study, leveraging microalgae as natural oxygenerators, provides a versatile and universal strategy for the development of oxygen-dependent tumor therapies.

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In vivo evaluation of the effects of combined boron and gadolinium neutron capture therapy in mouse models

Cited by 7 publications

References 22 publications

Synthesis and Characterization of Gd-Functionalized B4C Nanoparticles for BNCT Applications

Synthesis and Characterization of Gd-Functionalized B4C Nanoparticles for BNCT Applications

Development of a Gadolinium–Boron-Conjugated Albumin for MRI-Guided Neutron Capture Therapy

In Situ Formed Microalgae-Integrated Living Hydrogel for Enhanced Tumor Starvation Therapy and Immunotherapy through Photosynthetic Oxygenation

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