Motexafin gadolinium: a novel radiosensitizer for brain tumors

Francis, Dave; Richards, Gregory M.; Forouzannia, Afshin; Mehta, Minesh P.; Khuntia, Deepak

doi:10.1517/14656560903179325

Cited by 15 publications

(10 citation statements)

References 43 publications

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“…Although anticancer drugs with direct ROS-accumulating activity have been shown to be effective for treating different types of cancer, the effects on normal cells are still controversial as they damage not only cancer cells but also normal cells. For instance, the radiosensitizer motexafin gadolinium interrupts the DNA repair process and causes injuries to surrounding normal cells [91]. Additionally, anthracyclines induce cardiotoxicity since their metabolites (e.g., oxygencentered free radicals) can cause heart failure or cardiomyopathy, with a higher risk for younger patients [92][93][94].…”

Section: Application Of Ros Induction For Anticancer Strategiesmentioning

confidence: 99%

Understanding of ROS-Inducing Strategy in Anticancer Therapy

Kim

Seo

2019

Oxidative Medicine and Cellular Longevity

288

193

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Redox homeostasis is essential for the maintenance of diverse cellular processes. Cancer cells have higher levels of reactive oxygen species (ROS) than normal cells as a result of hypermetabolism, but the redox balance is maintained in cancer cells due to their marked antioxidant capacity. Recently, anticancer therapies that induce oxidative stress by increasing ROS and/or inhibiting antioxidant processes have received significant attention. The acceleration of accumulative ROS disrupts redox homeostasis and causes severe damage in cancer cells. In this review, we describe ROS-inducing cancer therapy and the anticancer mechanism employed by prooxidative agents. To understand the comprehensive biological response to certain prooxidative anticancer drugs such as 2-methoxyestradiol, buthionine sulfoximine, cisplatin, doxorubicin, imexon, and motexafin gadolinium, we propose and visualize the drug-gene, drug-cell process, and drug-disease interactions involved in oxidative stress induction and antioxidant process inhibition as well as specific side effects of these drugs using pathway analysis with a big data-based text-mining approach. Our review will be helpful to improve the therapeutic effects of anticancer drugs by providing information about biological changes that occur in response to prooxidants. For future directions, there is still a need for pharmacogenomic studies on prooxidative agents as well as the molecular mechanisms underlying the effects of the prooxidants and/or antioxidant-inhibitor agents for effective anticancer therapy through selective killing of cancer cells.

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Section: Application Of Ros Induction For Anticancer Strategiesmentioning

confidence: 99%

Understanding of ROS-Inducing Strategy in Anticancer Therapy

Kim

Seo

2019

Oxidative Medicine and Cellular Longevity

288

193

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“…Motexafin gadolinium (MGd), a metallotexaphyrin, can catalyze the oxidation of intracellular reducing metabolites and generate ROS. Several large studies demonstrated that MGd was capable of potentially enhancing the cytotoxic effects of radiation through several mechanisms as well as selectively inhibiting tumor cell growth by itself 68 . Consequently, Gd-based agents show great promise for multifunctional theranostic (diagnostic and therapeutic) applications in clinical practice.…”

Section: Metal-based Nanoenhancers For Ionizing Ramentioning

confidence: 99%

Metal-based NanoEnhancers for Future Radiotherapy: Radiosensitizing and Synergistic Effects on Tumor Cells

et al. 2018

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Radiotherapy is one of the major therapeutic strategies for cancer treatment. In the past decade, there has been growing interest in using high Z (atomic number) elements (materials) as radiosensitizers. New strategies in nanomedicine could help to improve cancer diagnosis and therapy at cellular and molecular levels. Metal-based nanoparticles usually exhibit chemical inertness in cellular and subcellular systems and may play a role in radiosensitization and synergistic cell-killing effects for radiation therapy. This review summarizes the efficacy of metal-based NanoEnhancers against cancers in both in vitro and in vivo systems for a range of ionizing radiations including gamma-rays, X-rays, and charged particles. The potential of translating preclinical studies on metal-based nanoparticles-enhanced radiation therapy into clinical practice is also discussed using examples of several metal-based NanoEnhancers (such as CYT-6091, AGuIX, and NBTXR3). Also, a few general examples of theranostic multimetallic nanocomposites are presented, and the related biological mechanisms are discussed.

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“… 37 Although MGd does not cross the blood–brain barrier (BBB) in healthy brains, MRI revealed its uptake in the brain tumour tissue of glioblastoma multiform (GBM) patients. 38 The reported MGd mechanism of action is thought to be less significantly modulated by the high atomic number of gadolinium in MGd, but rather more directly associated with complex biochemical processes. This is accounted for by its sensitization of cells through oxidative stress caused by redox cycling, leading to an enhanced radiation response.…”

Section: Gadolinium a Key Element At The Juncture Between Imaging Anmentioning

confidence: 99%

The use of theranostic gadolinium-based nanoprobes to improve radiotherapy efficacy

Sancey¹,

Lux²,

Kotb³

et al. 2014

BJR

184

197

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A new efficient type of gadolinium-based theranostic agent (AGuIX®) has recently been developed for MRI-guided radiotherapy (RT). These new particles consist of a polysiloxane network surrounded by a number of gadolinium chelates, usually 10. Owing to their small size (<5 nm), AGuIX typically exhibit biodistributions that are almost ideal for diagnostic and therapeutic purposes. For example, although a significant proportion of these particles accumulate in tumours, the remainder is rapidly eliminated by the renal route. In addition, in the absence of irradiation, the nanoparticles are well tolerated even at very high dose (10 times more than the dose used for mouse treatment). AGuIX particles have been proven to act as efficient radiosensitizers in a large variety of experimental in vitro scenarios, including different radioresistant cell lines, irradiation energies and radiation sources (sensitizing enhancement ratio ranging from 1.1 to 2.5). Pre-clinical studies have also demonstrated the impact of these particles on different heterotopic and orthotopic tumours, with both intratumoural or intravenous injection routes. A significant therapeutical effect has been observed in all contexts. Furthermore, MRI monitoring was proven to efficiently aid in determining a RT protocol and assessing tumour evolution following treatment. The usual theoretical models, based on energy attenuation and macroscopic dose enhancement, cannot account for all the results that have been obtained. Only theoretical models, which take into account the Auger electron cascades that occur between the different atoms constituting the particle and the related high radical concentrations in the vicinity of the particle, provide an explanation for the complex cell damage and death observed.

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Motexafin gadolinium: a novel radiosensitizer for brain tumors

Cited by 15 publications

References 43 publications

Understanding of ROS-Inducing Strategy in Anticancer Therapy

Understanding of ROS-Inducing Strategy in Anticancer Therapy

Metal-based NanoEnhancers for Future Radiotherapy: Radiosensitizing and Synergistic Effects on Tumor Cells

The use of theranostic gadolinium-based nanoprobes to improve radiotherapy efficacy

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