Nanostructured Boron Compounds for Boron Neutron Capture Therapy (BNCT) in Cancer Treatment

Gao, Shanmin; Zhu, Yongwei; Hosmane, Narayan S.

doi:10.1002/9781119275602.ch3.4

Cited by 13 publications

(8 citation statements)

References 66 publications

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“…Researchers tried to overcome this problem by developing boron-containing nanoparticles for delivering at least 20 ppm of boron to the tumor cells [61,69]. Some of the developed boron-containing nanoparticles have significantly improved the delivery efficacy of boron to the tumor cells and exhibited excellent tumor destruction in animal models [61,70].…”

Section: Development Of Novel Bnct Agentsmentioning

confidence: 99%

Boron Chemistry for Medical Applications

2020

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Boron compounds now have many applications in a number of fields, including Medicinal Chemistry. Although the uses of boron compounds in pharmacological science have been recognized several decades ago, surprisingly few are found in pharmaceutical drugs. The boron-containing compounds epitomize a new class for medicinal chemists to use in their drug designs. Carboranes are a class of organometallic compounds containing carbon (C), boron (B), and hydrogen (H) and are the most widely studied boron compounds in medicinal chemistry. Additionally, other boron-based compounds are of great interest, such as dodecaborate anions, metallacarboranes and metallaboranes. The boron neutron capture therapy (BNCT) has been utilized for cancer treatment from last decade, where chemotherapy and radiation have their own shortcomings. However, the improvement in the already existing (BPA and/or BSH) localized delivery agents or new tumor-targeted compounds are required before realizing the full clinical potential of BNCT. The work outlined in this short review addresses the advancements in boron containing compounds. Here, we have focused on the possible clinical implications of the new and improved boron-based biologically active compounds for BNCT that are reported to have in vivo and/or in vitro efficacy.

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Section: Development Of Novel Bnct Agentsmentioning

confidence: 99%

Boron Chemistry for Medical Applications

2020

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“…Other examples of nanosystems engineered for boron delivery into tumour tissue have been reported and recently reviewed [76]. Different degrees of tumour accumulation have been achieved in different tumour models and experimental approaches.…”

Section: Resultsmentioning

confidence: 99%

Gold Nanoparticles as Boron Carriers for Boron Neutron Capture Therapy: Synthesis, Radiolabelling and In Vivo Evaluation

et al. 2019

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Background: Boron Neutron Capture Therapy (BNCT) is a binary approach to cancer therapy that requires accumulation of boron atoms preferentially in tumour cells. This can be achieved by using nanoparticles as boron carriers and taking advantage of the enhanced permeability and retention (EPR) effect. Here, we present the preparation and characterization of size and shape-tuned gold NPs (AuNPs) stabilised with polyethylene glycol (PEG) and functionalized with the boron-rich anion cobalt bis(dicarbollide), commonly known as COSAN. The resulting NPs were radiolabelled with 124I both at the core and the shell, and were evaluated in vivo in a mouse model of human fibrosarcoma (HT1080 cells) using positron emission tomography (PET). Methods: The thiolated COSAN derivatives for subsequent attachment to the gold surface were synthesized by reaction of COSAN with tetrahydropyran (THP) followed by ring opening using potassium thioacetate (KSAc). Iodination on one of the boron atoms of the cluster was also carried out to enable subsequent radiolabelling of the boron cage. AuNPs grafted with mPEG-SH (5 Kda) and thiolated COSAN were prepared by ligand displacement. Radiolabelling was carried out both at the shell (isotopic exchange) and at the core (anionic absorption) of the NPs using 124I to enable PET imaging. Results: Stable gold nanoparticles simultaneously functionalised with PEG and COSAN (PEG-AuNPs@[4]−) with hydrodynamic diameter of 37.8 ± 0.5 nm, core diameter of 19.2 ± 1.4 nm and ξ-potential of −18.0 ± 0.7 mV were obtained. The presence of the COSAN on the surface of the NPs was confirmed by Raman Spectroscopy and UV-Vis spectrophotometry. PEG-AuNPs@[4]− could be efficiently labelled with 124I both at the core and the shell. Biodistribution studies in a xenograft mouse model of human fibrosarcoma showed major accumulation in liver, lungs and spleen, and poor accumulation in the tumour. The dual labelling approach confirmed the in vivo stability of the PEG-AuNPs@[4]−. Conclusions: PEG stabilized, COSAN-functionalised AuNPs could be synthesized, radiolabelled and evaluated in vivo using PET. The low tumour accumulation in the animal model assayed points to the need of tuning the size and geometry of the gold core for future studies.

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“…Due to their size (100–300 nm), functionalized CNTs avoid uptake by the RES prolonging their circulation in the blood stream as well as improving their bioavailability. Gao and co-workers designed nido -carborane units supported on water-soluble single-walled CNTs [ 111 ]. These nanocomposites were tumor specific, delivering 21.5 µg 10 B/g into the tumor within 48 h of administration.…”

Section: Boron-containing Nanoparticlesmentioning

confidence: 99%

“…Boron nitride nanotubes (BNNTs), which are structural analogs of CNTs, have been considered as a better alternative candidate for BNCT applications. BNNTs feature high boron density (approximately 50%) equivalent to hundreds or thousands for each nanotube [ 111 , 112 ]. Further, boron-enriched BNNTs have superior thermal and chemical stability compared to CNTs, in addition to their ability to resist oxidation and superior biocompatibility [ 13 ].…”

Section: Boron-containing Nanoparticlesmentioning

confidence: 99%

Multi-Functional Boron-Delivery Agents for Boron Neutron Capture Therapy of Cancers

Oloo,

Smith,

Vicente

2023

Cancers

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Boron neutron capture therapy (BNCT) is a binary cancer treatment that involves the irradiation of 10B-containing tumors with low-energy neutrons (thermal or epithermal). The alpha particles and recoiling Li nuclei that are produced in the 10B-capture nuclear reaction are high-linear-energy transfer particles that destroy boron-loaded tumor cells; therefore, BNCT has the potential to be a localized therapeutic modality. Two boron-delivery agents have been used in clinical trials of BNCT in patients with malignant brain tumors, cutaneous melanoma, or recurrent tumors of the head and neck region, demonstrating the potential of BNCT in the treatment of difficult cancers. A variety of potentially highly effective boron-delivery agents have been synthesized in the past four decades and tested in cells and animal models. These include boron-containing nucleosides, peptides, proteins, polyamines, porphyrins, liposomes, monoclonal antibodies, and nanoparticles of various types. The most promising agents are multi-functional boronated molecules and nanoparticles functionalized with tumor cell-targeting moieties that increase their tumor selectivity and contain a radiolabel or fluorophore to allow quantification of 10B-biodistribution and treatment planning. This review discusses multi-functional boron agents reported in the last decade, but their full potential can only be ascertained after their evaluation in BNCT clinical trials.

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Nanostructured Boron Compounds for Boron Neutron Capture Therapy (BNCT) in Cancer Treatment

Cited by 13 publications

References 66 publications

Boron Chemistry for Medical Applications

Boron Chemistry for Medical Applications

Gold Nanoparticles as Boron Carriers for Boron Neutron Capture Therapy: Synthesis, Radiolabelling and In Vivo Evaluation

Multi-Functional Boron-Delivery Agents for Boron Neutron Capture Therapy of Cancers

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