Nanoparticle-mediated knockdown of DNA repair sensitizes cells to radiotherapy and extends survival in a genetic mouse model of glioblastoma

Kievit, Forrest M.; Wang, Kui; Ozawa, Tatsuya; Tarudji, Aria W.; Silber, John R.; Holland, Eric C.; Ellenbogen, Richard G.; Zhang, Miqin

doi:10.1016/j.nano.2017.06.004

Cited by 38 publications

(45 citation statements)

References 41 publications

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“…This is potentially an effective therapy for human glioblastoma and warrants further study in vivo . Knockdown of DNA repair protein apurinic endonuclease 1 by nanoparticle-based delivery of a siRNA has been demonstrated to increase sensitivity to radiotherapy in a genetic mouse model of glioblastoma resulting in prolonged survival ( 94 ).…”

Section: Rna Interference Therapy Of Glioblastomamentioning

confidence: 99%

A Critical Overview of Targeted Therapies for Glioblastoma

2018

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Over the past century, treatment of malignant tumors of the brain has remained a challenge. Refinements in neurosurgical techniques, discovery of powerful chemotherapeutic agents, advances in radiotherapy, applications of biotechnology, and improvements in methods of targeted delivery have led to some extension of length of survival of glioblastoma patients. Refinements in surgery are mentioned because most of the patients with glioblastoma undergo surgery and many of the other innovative therapies are combined with surgery. However, cure of glioblastoma has remained elusive because it requires complete destruction of the tumor. Radical surgical ablation is not possible in the brain and even a small residual tumor leads to rapid recurrence that eventually kills the patient. Blood-brain barrier (BBB) comprising brain endothelial cells lining the cerebral microvasculature, limits delivery of drugs to the brain. Even though opening of the BBB in tumor core occurs locally, BBB limits systemic chemotherapy especially at the tumor periphery, where tumor cells invade normal brain structure comprising intact BBB. Comprehensive approaches are necessary to gain maximally from promising targeted therapies. Common methods used for critical evaluation of targeted therapies for glioblastoma include: (1) novel methods for targeted delivery of chemotherapy; (2) strategies for delivery through BBB and blood-tumor barriers; (3) innovations in radiotherapy for selective destruction of tumor; (4) techniques for local destruction of tumor; (5) tumor growth inhibitors; (6) immunotherapy; and (7) cell/gene therapies. Suggestions for improvements in glioblastoma therapy include: (1) controlled targeted delivery of anticancer therapy to glioblastoma through the BBB using nanoparticles and monoclonal antibodies; (2) direct introduction of genetically modified bacteria that selectively destroy cancer cells but spare the normal brain into the remaining tumor after resection; (3) use of better animal models for preclinical testing; and (4) personalized/precision medicine approaches to therapy in clinical trials and translation into practice of neurosurgery and neurooncology. Advances in these techniques suggest optimism for the future management of glioblastoma.

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Section: Rna Interference Therapy Of Glioblastomamentioning

confidence: 99%

A Critical Overview of Targeted Therapies for Glioblastoma

2018

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“…The therapy has been tested in different situations and developed via animal, cell, and human modeling. Various tests have been conducted, and their outcomes are described below to explain the recent developments that have taken place in the field (McCarroll et al, 2014;Clift et al, 2015;Kievit et al, 2017;Zavaleta et al, 2018).…”

Section: Nanotheranostics and Its Development In The Context Of Neuromentioning

confidence: 99%

Nanotheranostic Applications for Detection and Targeting Neurodegenerative Diseases

Kumar

Chaudhary²,

Singh

et al. 2020

Front. Neurosci.

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Nanotechnology utilizes engineered materials and devices which function with biological systems at the molecular level and could transform the management of neurodegenerative diseases (NDs) by provoking, reacting to, and intermingling with target sites to stimulate physiological responses while minimizing side effects. Bloodbrain barrier (BBB) protects the brain from harmful agents, and transporting drugs across the BBB is a major challenge for diagnosis, targeting, and treatment of NDs. The BBB provides severe limitations for diagnosis and treatment of Alzheimer's disease (AD), Parkinson's disease (PD), and various other neurological diseases. Conventional drug delivery systems generally fail to cross the BBB, thus are inefficient in treatment. Although gradual development through research is ensuring the progress of nanotheranostic approaches from animal to human modeling, aspects of translational applicability and safety are a key concern. This demands a deep understanding of the interaction of body systems with nanomaterials. There are various plant-based nanobioactive compounds which are reported to have applicability in the diagnosis and treatment of these NDs. This review article provides an overview of applications of nanotheranostics in AD and PD. The review also discusses nano-enabled drug delivery systems and their current and potential applications for the treatment of various NDs.

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“…Apurinic endonuclease 1 (Ape1) is an enzyme involved in base excision repair. The SPION (4-6 nm)-based siRNA delivery system knocked down the expression of Ape1 and sensitized brain tumor cells to radiotherapy [97,109].…”

Section: Nanoradiosensitizers Based On Dna Damagementioning

confidence: 99%

The Rational Design and Biological Mechanisms of Nanoradiosensitizers

2020

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Radiotherapy (RT) has been widely used for cancer treatment. However, the intrinsic drawbacks of RT, such as radiotoxicity in normal tissues and tumor radioresistance, promoted the development of radiosensitizers. To date, various kinds of nanoparticles have been found to act as radiosensitizers in cancer radiotherapy. This review focuses on the current state of nanoradiosensitizers, especially the related biological mechanisms, and the key design strategies for generating nanoradiosensitizers. The regulation of oxidative stress, DNA damage, the cell cycle, autophagy and apoptosis by nanoradiosensitizers in vitro and in vivo is highlighted, which may guide the rational design of therapeutics for tumor radiosensitization.

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Nanoparticle-mediated knockdown of DNA repair sensitizes cells to radiotherapy and extends survival in a genetic mouse model of glioblastoma

Cited by 38 publications

References 41 publications

A Critical Overview of Targeted Therapies for Glioblastoma

A Critical Overview of Targeted Therapies for Glioblastoma

Nanotheranostic Applications for Detection and Targeting Neurodegenerative Diseases

The Rational Design and Biological Mechanisms of Nanoradiosensitizers

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