Toward a cancer therapy with boron-rich oligomeric phosphate diesters that target the cell nucleus

Nakanishi, Akira; Guan, Lufeng; Kane, Robert R.; Kasamatsu, Harumi; Hawthorne, M. Frederick

doi:10.1073/pnas.96.1.238

Cited by 45 publications

(21 citation statements)

References 14 publications

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“…33 10 12 atoms/cell, respectively. From this result, we confirmed that these liposomes can deliver sufficient amount of boron 10 8 -10 9 10 B atoms/tumor cell to B16 melanoma cells for effective BNCT 33 .…”

Section: In Vitro Release Of Polyborane From Liposomessupporting

confidence: 66%

Polyborane-encapsulated PEGylated Liposomes Prepared Using Post-insertion Technique for Boron Neutron Capture Therapy

et al. 2019

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Introduction Research on liposomes as drug carriers for cancer treatment has been widely conducted. Liposomes are closed vesicles formed of phospholipids which are basic components of biomembrane. They can encapsulate the lipophilic drug within the lipid bilayer and the hydrophilic drug within the aqueous core. In addition, it is also possible to incorporate both types of drugs into the same liposome formulation 1. PEGylation of liposomes has been frequently used to efficiently deliver drugs to tumors. PEGylation has the ability to decrease uptake by reticuloendothelial system, prolong blood retention, decrease degradation by metabolic enzymes, and reduce protein immunogenicity 2, 3. Strategies utilizing this are known to be useful for passive and active targeting to tumor cells 2 4. In the conventional PEG modification method, PEG lipid is added before liposome formation pre-insertion. However, this method has the problem that PEG is also modified on the membrane

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Section: In Vitro Release Of Polyborane From Liposomessupporting

confidence: 66%

Polyborane-encapsulated PEGylated Liposomes Prepared Using Post-insertion Technique for Boron Neutron Capture Therapy

et al. 2019

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“…Other nuclear-targeting molecules are nido-carboranyl oligomeric phosphate diesters. Despite their multiple negative charges, oligomeric phosphate diesters have been shown to target the nuclei of TC7 cells following microinjection (69), suggesting that the combination of oligomeric phosphate diesters with a celltargeting molecule capable of crossing the plasma membrane could provide both selectivity and nuclear binding. Such a conjugate recently has been designed and synthesized (70), although its biological evaluation has yet to be reported.…”

Section: Low Molecular Weight Agentsmentioning

confidence: 99%

Boron Neutron Capture Therapy of Cancer: Current Status and Future Prospects

Barth

Coderre²,

Vicente³

et al. 2005

Clinical Cancer Research

912

666

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Background: Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when boron-10 is irradiated with low-energy thermal neutrons to yield high linear energy transfer A particles and recoiling lithium-7 nuclei. Clinical interest in BNCT has focused primarily on the treatment of high-grade gliomas and either cutaneous primaries or cerebral metastases of melanoma, most recently, head and neck and liver cancer. Neutron sources for BNCT currently are limited to nuclear reactors and these are available in the United States, Japan, several European countries, and Argentina. Accelerators also can be used to produce epithermal neutrons and these are being developed in several countries, but none are currently being used for BNCT. Boron Delivery Agents: Two boron drugs have been used clinically, sodium borocaptate (Na 2 B 12 H 11 SH) and a dihydroxyboryl derivative of phenylalanine called boronophenylalanine. The major challenge in the development of boron delivery agents has been the requirement for selective tumor targeting to achieve boron concentrations (f20 Ag/g tumor) sufficient to deliver therapeutic doses of radiation to the tumor with minimal normal tissue toxicity. Over the past 20 years, other classes of boron-containing compounds have been designed and synthesized that include boroncontaining amino acids, biochemical precursors of nucleic acids, DNA-binding molecules, and porphyrin derivatives. High molecular weight delivery agents include monoclonal antibodies and their fragments, which can recognize a tumor-associated epitope, such as epidermal growth factor, and liposomes. However, it is unlikely that any single agent will target all or even most of the tumor cells, and most likely, combinations of agents will be required and their delivery will have to be optimized. Clinical Trials: Current or recently completed clinical trials have been carried out inJapan, Europe, and the United States. The vast majority of patients have had high-grade gliomas. Treatment has consisted first of ''debulking'' surgery to remove as much of the tumor as possible, followed by BNCTat varying times after surgery. Sodium borocaptate and boronophenylalanine administered i.v have been used as the boron delivery agents. The best survival data from these studies are at least comparable with those obtained by current standard therapy for glioblastoma multiforme, and the safety of the procedure has been established. Conclusions: Critical issues that must be addressed include the need for more selective and effective boron delivery agents, the development of methods to provide semiquantitative estimates of tumor boron content before treatment, improvements in clinical implementation of BNCT, and a need for randomized clinical trials with an unequivocal demonstration of therapeutic efficacy. If these issues are adequately addressed, then BNCTcould move forward as a treatment modality.

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“…Other nuclear-targeting molecules are nido-carboranyl oligomeric phosphate diesters (OPDs). Despite their multiple negative charges, OPDs have been shown to target the nuclei of TC7 cells following microinjection (74), suggesting that the combination of OPDs with a cell-targeting molecule capable of crossing the plasma membrane could provide both selectivity and nuclear binding. Such a conjugate has been designed and synthesized (75), although its biological evaluation has yet to be reported.…”

Section: Biochemical Precursors and Dna Binding Agentsmentioning

confidence: 99%