Advancements in Tumor Targeting Strategies for Boron Neutron Capture Therapy

Luderer, Micah John; Puente, Pilar de la; Azab, Abdel Kareem

doi:10.1007/s11095-015-1718-y

Cited by 108 publications

(68 citation statements)

References 89 publications

(157 reference statements)

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“…Meanwhile, the application of bismuth NPs will be presented here. Although there is not a lot of data about the application of other metalloid NPs in medicine in cancer research in particular, to the best of the authors' knowledge, boron NPs have been used for different diagnosis or therapeutic purposes in cancer models [160,161], but other metalloid NPs such as germanium are frequently used in other areas of nanotechnology. Silicon NPs are also well-known as quantum dot (QD) agents and typically used for diagnostic systems [162].…”

Section: Metalloid Nanoparticles and Cancermentioning

confidence: 99%

Metal, Metalloid, and Oxide Nanoparticles for Therapeutic and Diagnostic Oncology

Yazdi¹,

Sepehrizadeh²,

Mahdavi³

et al. 2016

Nano BioMed ENG

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Nanoparticles have comprehensively affected various sights of human life. Through the wide range of claims about nanosized particles and their functions, biomedical applications are of much interest among health care researchers due to the nanoparticles' potential for use in the process of disease diagnosis, control and treatment. In this regard, inorganic nanoparticles, which have high potential in diagnostic and therapeutic systems, have recently received much attention in oncology. Although inorganic nanoparticles initially seemed an appropriate tool for cancer imaging and diagnosis, their ability to attack cancerous cells as anticancer drugs or carriers in other drugs has also demonstrated promising results. The present review primarily provides a brief survey of various studies in which metal nanoparticles such as gold, silver, iron oxide, and metalloid nanoparticles viz. tellurium and bismuth were exploited for therapeutic or diagnostic purposes in oncology. Then the application of selenium nanoparticles as a therapeutic agent against cancer in in vitro and in vivo studies is reviewed in detail. Although inorganic nanoparticles seem to be useful tools for cancer imaging and diagnosis, their potential for attacking cancerous cells as anticancer substances or even carriers for anticancer medications should not be underestimated.

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Section: Metalloid Nanoparticles and Cancermentioning

confidence: 99%

Metal, Metalloid, and Oxide Nanoparticles for Therapeutic and Diagnostic Oncology

Yazdi¹,

Sepehrizadeh²,

Mahdavi³

et al. 2016

Nano BioMed ENG

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“…The resulting intracellular production of high-energy alpha particles can target tumor cells for destruction while having less off-target associated cytotoxicity compared to XRT and chemotherapy (6, 7). However, the potential of BNCT to have a targeted tumoricidal effect is limited by the ability of a boronated agent to accumulate specifically in the tumor (ideally T/N > 3).…”

Section: Discussionmentioning

confidence: 99%

“…BNCT utilizes the neutron capture reaction of boron-10 ( 10 B) and its subsequent nuclear fission reaction to produce cellular death (7). After a 10 B atom absorbs a neutron, the resulting unstable 11 B isotope undergoes a nuclear fission reaction releasing an alpha particle, lithium-7 ion and gamma radiation (8).…”

Section: Introductionmentioning

confidence: 99%

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A Hypoxia-Targeted Boron Neutron Capture Therapy Agent for the Treatment of Glioma

et al. 2016

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Purpose Boron neutron capture therapy (BNCT) has the potential to become a viable cancer treatment modality, but its clinical translation has been limited by the poor tumor selectivity of agents. To address this unmet need, a boronated 2-nitroimidazole derivative (B-381) was synthesized and evaluated for its capability of targeting hypoxic glioma cells. Methods B-381 has been synthesized from a 1-step reaction. Using D54 and U87 glioma cell lines, the in vitro cytotoxicity and cellular accumulation of B-381 has been evaluated under normoxic and hypoxic conditions compared to L-boronophenylalanine (BPA). Furthermore, tumor retention of B-381 was evaluated in vivo. Results B-381 had low cytotoxicity in normal and cancer cells. Unlike BPA, B-381 illustrated preferential retention in hypoxic glioma cells compared to normoxic glioma cells and normal tissues in vitro. In vivo, B-381 illustrated significantly higher long-term tumor retention compared to BPA, with 9.5-fold and 6.5-fold higher boron levels at 24 and 48 h, respectively. Conclusions B-381 represents a new class of BNCT agents in which their selectivity to tumors is based on tumor hypoxic metabolism, and further studies are warranted to evaluate this compound and similar compounds as preclinical candidates for future BNCT clinical trials for the treatment of glioma.

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“…Despite their clinical use and the safe and effective BNCT, trials performed with these two drugs until now, both BPA and BSH show low selectivity and great efforts have been made by several research groups to develop new and more selective boron delivery agents [11][12].The use of BNCT to destroy malignant cells was proposed long time ago [13]. In spite of huge promises, it has not attained an established position in the mainstream medicine.…”

Section: B and 157mentioning

confidence: 99%

Insights into the Use of Gadolinium and Gadolinium/Boron-Based Agents in Imaging-Guided Neutron Capture Therapy Applications

et al. 2016

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Gadolinium neutron capture therapy (Gd-NCT) is currently under development as an alternative approach for cancer therapy. All of the clinical experience to date with NCT is done with 10 B, known as BNCT, a binary treatment combining neutron irradiation with the delivery of boron-containing compounds to tumors. Currently, the use of gadolinium for NCT has been getting more attention because of its highest neutron cross-section. Although Gd-NCT was first proposed many years ago, its development has suffered due to lack of appropriate tumor-selective Gd-agents. This review aims to highlight the recent advances for the design, synthesis and biological testing of new Gd-and B-Gd-containing compounds with the task of finding the best systems able to improve the NCT clinical outcome. Keywords:Gadolinium Neutron Capture Therapy, Boron Neutron Capture Therapy, MRI, Gd contrast agents, Tumor Treatment, Nanosized Gd agents. 3 General introduction on NCT: rationale and applicationNeutron Capture Therapy (NCT) is a non-conventional radiotherapy that combines low energy neutron irradiation with the presence of a neutron-absorbing substance at the targeted cells [1][2].Two isotopes are of major interest because of their large capture cross section: head and neck recurrent cancer [6][7], melanoma [8] and adenocarcinoma liver metastases [9]; ii) sodium mercaptoundecahydro-closo-dodecaborate (BSH) that has been investigated for the treatment of malignant glioma [10]. Despite their clinical use and the safe and effective BNCT, trials performed with these two drugs until now, both BPA and BSH show low selectivity and great efforts have been made by several research groups to develop new and more selective boron delivery agents [11][12].The use of BNCT to destroy malignant cells was proposed long time ago [13]. In spite of huge promises, it has not attained an established position in the mainstream medicine.However, the methodology has never been discarded and it remains in an intermediate state with a small group of enthusiast supporters and many critical spectators. The reasons why BNCT has not maintained the original promises rely mainly in the lack of properly designed agents. The conditions for an effective therapeutic output are well established: the BNCT agent must reach selectively a given concentration inside cells and the not-attainment of this task makes the therapy less effective. Only a proper NCT agent design (based on an improved knowledge on how molecules enter healthy and diseased cells) allows to reach selectively the needed threshold of intracellular concentration required to drive the breakthrough of BNCT in the field of conventional and diffused treatments for cancer. Moreover, the in vivo assessment of the amount of NCT agent can now be tackled by its conjugation to a suitable imaging-reporter. [14][15] To date there is no non-invasive means to evaluate boron concentration in tumor and healthy tissues of the subject undergoing the irradiation. Thus, dose calculations are based on boron content values in...

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Advancements in Tumor Targeting Strategies for Boron Neutron Capture Therapy

Cited by 108 publications

References 89 publications

Metal, Metalloid, and Oxide Nanoparticles for Therapeutic and Diagnostic Oncology

Metal, Metalloid, and Oxide Nanoparticles for Therapeutic and Diagnostic Oncology

A Hypoxia-Targeted Boron Neutron Capture Therapy Agent for the Treatment of Glioma

Insights into the Use of Gadolinium and Gadolinium/Boron-Based Agents in Imaging-Guided Neutron Capture Therapy Applications

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