Recommendations for In Vitro and In Vivo Testing of Magnetic Nanoparticle Hyperthermia Combined with Radiation Therapy  †

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Abstract

Magnetic nanoparticle (MNP)-mediated hyperthermia (MH) coupled with radiation therapy (RT) is a novel approach that has the potential to overcome various practical difficulties encountered in cancer treatment. In this work, we present recommendations for the in vitro and in vivo testing and application of the two treatment techniques. These recommendations were developed by the members of Working Group 3 of COST Action TD 1402: Multifunctional Nanoparticles for Magnetic Hyperthermia and Indirect Radiation Therapy (“Radiomag”). The purpose of the recommendations is not to provide definitive answers and directions but, rather, to outline those tests and considerations that a researcher must address in order to perform in vitro and in vivo studies. The recommendations are divided into 5 parts: (a) in vitro evaluation of MNPs; (b) in vitro evaluation of MNP-cell interactions; (c) in vivo evaluation of the MNPs; (d) MH combined with RT; and (e) pharmacokinetic studies of MNPs. Synthesis and characterization of the MNPs, as well as RT protocols, are beyond the scope of this work.

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Hyperthermia in combined treatment of cancer.

P Wust, B Hildebrandt, G. Sreenivasa … (2002)

Hyperthermia, the procedure of raising the temperature of tumour-loaded tissue to 40-43 degrees C, is applied as an adjunctive therapy with various established cancer treatments such as radiotherapy and chemotherapy. The potential to control power distributions in vivo has been significantly improved lately by the development of planning systems and other modelling tools. This increased understanding has led to the design of multiantenna applicators (including their transforming networks) and implementation of systems for monitoring of E-fields (eg, electro-optical sensors) and temperature (particularly, on-line magnetic resonance tomography). Several phase III trials comparing radiotherapy alone or with hyperthermia have shown a beneficial effect of hyperthermia (with existing standard equipment) in terms of local control (eg, recurrent breast cancer and malignant melanoma) and survival (eg, head and neck lymph-node metastases, glioblastoma, cervical carcinoma). Therefore, further development of existing technology and elucidation of molecular mechanisms are justified. In recent molecular and biological investigations there have been novel applications such as gene therapy or immunotherapy (vaccination) with temperature acting as an enhancer, to trigger or to switch mechanisms on and off. However, for every particular temperature-dependent interaction exploited for clinical purposes, sophisticated control of temperature, spatially as well as temporally, in deep body regions will further improve the potential.

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Radiotherapy and immunotherapy: a beneficial liaison?

Ralph Weichselbaum, Wen-Hua Liang, Liufu Deng … (2017)

The interaction between radiotherapy and the host immune system has uncovered new mechanisms that can be exploited to improve the efficacy of radiotherapy. In this article, the authors highlight data providing new explanations for the success or failure of radiotherapy, and postulate, using radiation-induced tumour equilibrium (RITE) as an example, how the combination of immune-modulation and radiation could tip the balance of the host immune response to promote cure.

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Normalizing tumor microenvironment to treat cancer: bench to bedside to biomarkers.

Rakesh Jain (2013)

For almost four decades, my work has focused on one challenge: improving the delivery and efficacy of anticancer therapeutics. Working on the hypothesis that the abnormal tumor microenvironment-characterized by hypoxia and high interstitial fluid pressure--fuels tumor progression and treatment resistance, we developed an array of sophisticated imaging technologies and animal models as well as mathematic models to unravel the complex biology of tumors. Using these tools, we demonstrated that the blood and lymphatic vasculature, fibroblasts, immune cells, and extracellular matrix associated with tumors are abnormal, which together create a hostile tumor microenvironment. We next hypothesized that agents that induce normalization of the microenvironment can improve treatment outcome. Indeed, we demonstrated that judicious use of antiangiogenic agents--originally designed to starve tumors--could transiently normalize tumor vasculature, alleviate hypoxia, increase delivery of drugs and antitumor immune cells, and improve the outcome of various therapies. Our trials of antiangiogenics in patients with newly diagnosed and recurrent glioblastoma supported this concept. They revealed that patients whose tumor blood perfusion increased in response to cediranib survived 6 to 9 months longer than those whose blood perfusion did not increase. The normalization hypothesis also opened doors to treating various nonmalignant diseases characterized by abnormal vasculature, such as neurofibromatosis type 2. More recently, we discovered that antifibrosis drugs capable of normalizing the tumor microenvironment can improve the delivery and efficacy of nano- and molecular medicines. Our current efforts are directed at identifying predictive biomarkers and more-effective strategies to normalize the tumor microenvironment for enhancing anticancer therapies.

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Author and article information

Journal

Journal ID (nlm-ta): Nanomaterials (Basel)

Journal ID (iso-abbrev): Nanomaterials (Basel)

Journal ID (publisher-id): nanomaterials

Title: Nanomaterials

Publisher: MDPI

ISSN (Electronic): 2079-4991

Publication date (Electronic): 06 May 2018

Publication date Collection: May 2018

Volume: 8

Issue: 5

Electronic Location Identifier: 306

Affiliations

[1 ]Department of Radiology, Sismanoglio General Hospital of Attica, Sismanogliou 1, 15126 Marousi, Athens, Greece

[2 ]LAQV, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal; slima@ 123456ff.up.pt (S.A.C.L.); up200800307@ 123456ff.up.pt (A.I.B.)

[3 ]Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research “Demokritos”, Aghia Paraskevi, 15310 Athens, Greece; bouzioti@ 123456rrp.demokritos.gr

[4 ]“Vinča” Institute of Nuclear Sciences, University of Belgrade, 11351 Belgrade, Serbia; sanjav@ 123456vinca.rs (S.V.-D.); drinaj@ 123456vinca.rs (D.J.)

[5 ]Inorganic Chemistry Laboratory, Chemistry Department, National and Kapodistrian University of Athens, Panepistimiopolis, 15784 Zografou, Greece; efthim@ 123456chem.chem.uoa.gr

[6 ]Institute of Nanoscience and Nanotechnology, NCSR Demokritos, Agia Paraskevi Attikis, 15310 Athens, Greece

[7 ]Department of Biomedical and Clinical Science “Mario Serio”, University of Florence, 50134 Firenze, Italy; anna.laurenzana@ 123456unifi.it

[8 ]Department of Surgery, Radiology & Ph.M. University of the Basque Country, E48940 Bilbao, Spain; ignacio.galonso@ 123456ehu.es

[9 ]NanoTherics Ltd., Studio 3, Unit 3, Silverdale Enterprise Centre Kents Lane, Newcastle under Lyme ST5 6SR, UK; carl.jones@ 123456nanotherics.com

[10 ]School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College Dublin, D02PN40 Dublin, Ireland

Author notes

[* ]Correspondence: spiridonspirou@ 123456yahoo.com (S.V.S.); ogobbo@ 123456tcd.ie (O.L.G.); Tel.: +30-213-2058-502 (S.V.S.); +353-1896-3181 (O.L.G.)

[†]

The authors dedicate this review article to the memory of our dearest friend and colleague Maria De Deus Carvalho, from the University of Lisbon, Portugal.

Author information

Spiridon V. Spirou https://orcid.org/0000-0003-3487-389X

Ignacio Garcia-Alonso https://orcid.org/0000-0002-3701-1761

Article

Publisher ID: nanomaterials-08-00306

DOI: 10.3390/nano8050306

PMC ID: 5977320

PubMed ID: 29734795

SO-VID: 2f3d7b66-9d63-4ddb-972c-929596a48420

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Recommendations for In Vitro and In Vivo Testing of Magnetic Nanoparticle Hyperthermia Combined with Radiation Therapy †

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Abstract

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Animal models of intrauterine growth restriction (IUGR)

Most cited references 150

Hyperthermia in combined treatment of cancer.

Radiotherapy and immunotherapy: a beneficial liaison?

Normalizing tumor microenvironment to treat cancer: bench to bedside to biomarkers.

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