Motexafin gadolinium: a promising radiation sensitizer in brain metastasis

Thomas, S.R.; Khuntia, Deepak

doi:10.1517/17460441.2011.546395

Cited by 18 publications

(11 citation statements)

References 51 publications

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“…In another, Motexafin gadolinium (Xcytrin) is expanded metalloporphyrin PS for the treatment of brain metastasis and lung cancer [ 41 , 42 ]. Motexafin gadolinium target to tumour cell than normal cell.…”

Section: Pss For Anticancer Pdtmentioning

confidence: 99%

Clinical development of photodynamic agents and therapeutic applications

2018

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BackgroundPhotodynamic therapy (PDT) is photo-treatment of malignant or benign diseases using photosensitizing agents, light, and oxygen which generates cytotoxic reactive oxygens and induces tumour regressions. Several photodynamic treatments have been extensively studied and the photosensitizers (PS) are key to their biological efficacy, while laser and oxygen allow to appropriate and flexible delivery for treatment of diseases.IntroductionIn presence of oxygen and the specific light triggering, PS is activated from its ground state into an excited singlet state, generates reactive oxygen species (ROS) and induces apoptosis of cancer tissues. Those PS can be divided by its specific efficiency of ROS generation, absorption wavelength and chemical structure.Main bodyUp to dates, several PS were approved for clinical applications or under clinical trials. Photofrin® is the first clinically approved photosensitizer for the treatment of cancer. The second generation of PS, Porfimer sodium (Photofrin®), Temoporfin (Foscan®), Motexafin lutetium, Palladium bacteriopheophorbide, Purlytin®, Verteporfin (Visudyne®), Talaporfin (Laserphyrin®) are clinically approved or under-clinical trials. Now, third generation of PS, which can dramatically improve cancer-targeting efficiency by chemical modification, nano-delivery system or antibody conjugation, are extensively studied for clinical development.ConclusionHere, we discuss up-to-date information on FDA-approved photodynamic agents, the clinical benefits of these agents. However, PDT is still dearth for the treatment of diseases in specifically deep tissue cancer. Next generation PS will be addressed in the future for PDT. We also provide clinical unmet need for the design of new photosensitizers.

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Section: Pss For Anticancer Pdtmentioning

confidence: 99%

Clinical development of photodynamic agents and therapeutic applications

2018

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“…Thus, it appears reasonable to propose that the inactivity of the synthesized iron complexes must be related to the impossibility of charged species to cross the cell membrane since iron conjugation confers a positive charge to the apolar nature of the ligands, leading to less lipid-soluble molecules with impaired ability to cross the cell membrane [ 62 ]. Conversely, neutral organic ligands can readily traverse the cell membrane and form the highly oxidizing iron complexes in situ [ 26 – 28 , 30 – 31 ].…”

Section: Discussionmentioning

confidence: 99%

Pro-Oxidant Activity of Amine-Pyridine-Based Iron Complexes Efficiently Kills Cancer and Cancer Stem-Like Cells

et al. 2015

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Differential redox homeostasis in normal and malignant cells suggests that pro-oxidant-induced upregulation of cellular reactive oxygen species (ROS) should selectively target cancer cells without compromising the viability of untransformed cells. Consequently, a pro-oxidant deviation well-tolerated by nonmalignant cells might rapidly reach a cell-death threshold in malignant cells already at a high setpoint of constitutive oxidative stress. To test this hypothesis, we took advantage of a selected number of amine-pyridine-based Fe(II) complexes that operate as efficient and robust oxidation catalysts of organic substrates upon reaction with peroxides. Five of these Fe(II)-complexes and the corresponding aminopyridine ligands were selected to evaluate their anticancer properties. We found that the iron complexes failed to display any relevant activity, while the corresponding ligands exhibited significant antiproliferative activity. Among the ligands, none of which were hemolytic, compounds 1, 2 and 5 were cytotoxic in the low micromolar range against a panel of molecularly diverse human cancer cell lines. Importantly, the cytotoxic activity profile of some compounds remained unaltered in epithelial-to-mesenchymal (EMT)-induced stable populations of cancer stem-like cells, which acquired resistance to the well-known ROS inducer doxorubicin. Compounds 1, 2 and 5 inhibited the clonogenicity of cancer cells and induced apoptotic cell death accompanied by caspase 3/7 activation. Flow cytometry analyses indicated that ligands were strong inducers of oxidative stress, leading to a 7-fold increase in intracellular ROS levels. ROS induction was associated with their ability to bind intracellular iron and generate active coordination complexes inside of cells. In contrast, extracellular complexation of iron inhibited the activity of the ligands. Iron complexes showed a high proficiency to cleave DNA through oxidative-dependent mechanisms, suggesting a likely mechanism of cytotoxicity. In summary, we report that, upon chelation of intracellular iron, the pro-oxidant activity of amine-pyrimidine-based iron complexes efficiently kills cancer and cancer stem-like cells, thus providing functional evidence for an efficient family of redox-directed anti-cancer metallodrugs.

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“…A small Gd(III)-complex designed for radiosensitization combined with MRI is porphyrin-like macrocycle motexafin gadolinium (MGd) ( Figure 2) that belongs to the texaphyrins class of drugs, which proved effective to mediate radiation of tumors and brain metastasis in particular [19]. A pre-clinical MRI study has revealed a selective uptake of MGd by malignant cells, most probably facilitated by the tumor pH being lower compared to those of healthy cells.…”

Section: Gadolinium-based Radiosensitizationmentioning

confidence: 99%

Potential of MRI in Radiotherapy Mediated by Small Conjugates and Nanosystems

2019

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Radiation therapy has made tremendous progress in oncology over the last decades due to advances in engineering and physical sciences in combination with better biochemical, genetic and molecular understanding of this disease. Local delivery of optimal radiation dose to a tumor, while sparing healthy surrounding tissues, remains a great challenge, especially in the proximity of vital organs. Therefore, imaging plays a key role in tumor staging, accurate target volume delineation, assessment of individual radiation resistance and even personalized dose prescription. From this point of view, radiotherapy might be one of the few therapeutic modalities that relies entirely on high-resolution imaging. Magnetic resonance imaging (MRI) with its superior soft-tissue resolution is already used in radiotherapy treatment planning complementing conventional computed tomography (CT). Development of systems integrating MRI and linear accelerators opens possibilities for simultaneous imaging and therapy, which in turn, generates the need for imaging probes with therapeutic components. In this review, we discuss the role of MRI in both external and internal radiotherapy focusing on the most important examples of contrast agents with combined therapeutic potential.

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Motexafin gadolinium: a promising radiation sensitizer in brain metastasis

Cited by 18 publications

References 51 publications

Clinical development of photodynamic agents and therapeutic applications

Clinical development of photodynamic agents and therapeutic applications

Pro-Oxidant Activity of Amine-Pyridine-Based Iron Complexes Efficiently Kills Cancer and Cancer Stem-Like Cells

Potential of MRI in Radiotherapy Mediated by Small Conjugates and Nanosystems

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