Tumor-specific delivery of BSH-3R for boron neutron capture therapy and positron emission tomography imaging in a mouse brain tumor model

Iguchi, Yoshiya; Michiue, Hiroyuki; Kitamatsu, Mizuki; Hayashi, Yoshihiro; Takenaka, Fumiaki; Nishiki, Tadaaki; Matsui, Hideki

doi:10.1016/j.biomaterials.2015.03.061

Cited by 61 publications

(42 citation statements)

References 34 publications

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“…Frequently used organisms are yeast ( Saccharomyces ) [27], Drosophila [28], Caenorhabditis elegans ( C. elegans ) [29], zebrafish [30], mouse [31], monkey [32], and many more. Drosophila or C. elegans are outstanding models for studying the events of genetic functions related to the common molecular machine.…”

Section: Different Model Organisms and Uniqueness Of Zebrafish Model mentioning

confidence: 99%

Zebrafish: A complete animal model to enumerate the nanoparticle toxicity

et al. 2016

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Presently, nanotechnology is a multi-trillion dollar business sector that covers a wide range of industries, such as medicine, electronics and chemistry. In the current era, the commercial transition of nanotechnology from research level to industrial level is stimulating the world’s total economic growth. However, commercialization of nanoparticles might offer possible risks once they are liberated in the environment. In recent years, the use of zebrafish (Danio rerio) as an established animal model system for nanoparticle toxicity assay is growing exponentially. In the current in-depth review, we discuss the recent research approaches employing adult zebrafish and their embryos for nanoparticle toxicity assessment. Different types of parameters are being discussed here which are used to evaluate nanoparticle toxicity such as hatching achievement rate, developmental malformation of organs, damage in gill and skin, abnormal behavior (movement impairment), immunotoxicity, genotoxicity or gene expression, neurotoxicity, endocrine system disruption, reproduction toxicity and finally mortality. Furthermore, we have also highlighted the toxic effect of different nanoparticles such as silver nanoparticle, gold nanoparticle, and metal oxide nanoparticles (TiO2, Al2O3, CuO, NiO and ZnO). At the end, future directions of zebrafish model and relevant assays to study nanoparticle toxicity have also been argued.

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Section: Different Model Organisms and Uniqueness Of Zebrafish Model mentioning

confidence: 99%

Zebrafish: A complete animal model to enumerate the nanoparticle toxicity

et al. 2016

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“…Only two compounds were used in clinical trials so far, namely l ‐boronophenylalanine (BPA) and sodium mercaptoundecahydro‐ closo ‐dodecaborate (BSH), but both are not optimal owing to insufficient tumor selectivity and low tumor retention times . Several new boron‐modified delivery vehicles have been developed, including nucleoside, amino acid, and porphyrin derivatives as well as antibody, polymer, protein, and cell penetrating peptide conjugates . Molecular‐targeted peptides are especially interesting as potential boron delivery agents due to their high affinity and selectivity.…”

Section: Introductionmentioning

confidence: 99%

“…[5][6][7][8] Several new boron-modified delivery vehicles have been Abbreviations: BNCT, boron neutron capture therapy; Dap, (2S)-2,3diaminopropionic acid; Dde, 4,4-dimethyl-2,6-dioxocyclohex-1-ylidenethyl; GhrR, ghrelin receptor; GPCR, G protein-coupled receptor; SPPS, solid phase peptide synthesis; TAMRA, 6-carboxytetramethylrhodamine developed, including nucleoside, amino acid, and porphyrin derivatives as well as antibody, polymer, protein, and cell penetrating peptide conjugates. [9][10][11][12][13][14][15][16][17] Molecular-targeted peptides are especially interesting as potential boron delivery agents due to their high affinity and selectivity. Such an approach was recently described by Kimura et al, who developed RGD-boron cluster conjugates for specific integrin binding.…”

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confidence: 99%

A stable meta‐carborane enables the generation of boron‐rich peptide agonists targeting the ghrelin receptor

Worm

Els‐Heindl

Kellert

et al. 2018

Journal of Peptide Science

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Boron neutron capture therapy (BNCT) is a binary cancer therapy, which combines the biochemical targeting of a boron-containing drug with the regional localization of radiation treatment. Although the concept of BNCT has been known for decades, the selective delivery of boron into tumor cells remains challenging. G protein-coupled receptors that are overexpressed on cancer cells in combination with peptidic ligands can be potentially used as shuttle system for a tumor-directed boron uptake. In this study, we present the generation of short, boron-rich peptide conjugates that target the ghrelin receptor. Expression of the ghrelin receptor on various cancer cells makes it a viable target for BNCT. We designed a novel hexapeptide super-agonist that was modified with different specifically synthesized carborane monoclusters and tested for ghrelin receptor activation. A meta-carborane building block with a mercaptoacetic acid linker was found to be optimal for peptide modification, owing to its chemical stability and a suitable activation efficacy of the conjugate. The versatility of this carborane for the development of peptidic boron delivery agents was further demonstrated by the generation of highly potent, boron-loaded conjugates using the backbone of the known ghrelin receptor ligands growth hormone releasing peptide 6 and Ipamorelin.

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“…Many recent results showed that a higher uptake of boron by tumor cells in vitro and in vivo when BSH was linked with biomaterials. Iquchi Y et al created a BSH fused with a short arginine peptide-labeled positron emission tomography (PET) probe, and the imaging results showed a high uptake in the tumor area [15]. Genady AR and his colleagues compounded a series of mono- and dicarboxyalkyl BSH derivatives, and found that BSH-conjugated triazole 15 induced a significant increase in the level of boron accumulation in HeLa cells [16].…”

Section: Discussionmentioning

confidence: 99%

Targeting glioma stem cells enhances anti-tumor effect of boron neutron capture therapy

Sun

Huang

et al. 2016

Oncotarget

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The uptake of (10)boron by tumor cells plays an important role for cell damage in boron neutron capture therapy (BNCT). CD133 is frequently expressed in the membrane of glioma stem cells (GSCs), resistant to radiotherapy and chemotherapy, and represents a potential therapeutic target. To increase (10)boron uptake in GSCs, we created a polyamido amine dendrimer, conjugated CD133 monoclonal antibodies, encapsulating mercaptoundecahydrododecaborate (BSH) in void spaces, and monitored the uptake of the bioconjugate nanoparticles by GSCs in vitro and in vivo. Fluorescence microscopy showed the specific uptake of the bioconjugate nanoparticles by CD133-positive GSCs. Treatment with the biconjugate nanoparticles resulted in a significant lethal effect after neutron radiation due to efficient and CD133-independent cellular targeting and uptake in CD133-expressing GSCs. A significantly longer survival occurred in combination with the biconjugate nanoparticles and BSH compared with BSH alone in human intracranial GBM models employing CD133-positive GSCs xenografts. Our data demonstrated that this bioconjugate nanoparticle targets human CD133-positive GSCs and is a potential boron agent in BNCT.

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Tumor-specific delivery of BSH-3R for boron neutron capture therapy and positron emission tomography imaging in a mouse brain tumor model

Cited by 61 publications

References 34 publications

Zebrafish: A complete animal model to enumerate the nanoparticle toxicity

Zebrafish: A complete animal model to enumerate the nanoparticle toxicity

A stable meta‐carborane enables the generation of boron‐rich peptide agonists targeting the ghrelin receptor

Targeting glioma stem cells enhances anti-tumor effect of boron neutron capture therapy

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