Deciphering intracellular events triggered by mild magnetic hyperthermia in vitro and in vivo

This work is licensed under the Creative Commons Attribution-NonCommercial 3.0 Unported License.-- et al.[Aim]: To assess the cell response to magnetic nanoparticles under an alternating magnetic field by molecular quantification of heat responsive transcripts in two model systems. [Materials & methods]: Melanoma cells and Hydra vulgaris treated with magnetic nanoparticles were subjected to an alternating magnetic field or to macroscopic heating. Effect to these treatments were assessed at animal, cellular and molecular levels. [Results]: By comparing hsp70 expression following both treatments, thermotolerance pathways were found in both systems in absence of cell ablation or global temperature increment. [Conclusion]: Analysis of hsp70 transcriptional activation can be used as molecular thermometer to sense cells' response to magnetic hyperthermia. Similar responses were found in cells and Hydra, suggesting a general mechanism to the delivery of sublethal thermal doses.The authors thank NanoSciEraNet project NANOTRUCK for financial support. JM de la Fuente thanks ERC-Starting Grant 239931-NANOPUZZLE project and Fondo Social Europeo (FSE; Gobierno de Aragón) for financial support.Peer Reviewe

Optically-Active Nanomaterials for Diagnostic and Therapeutic Applications in Ovarian Cancer

The clinical management of cancer has principally relied upon surgery, radiation therapy, and chemotherapy for many decades. Despite recent advances in molecularly-targeted diagnostic and therapeutic agents, the long-term survival rates in patients with solid malignancies including ovarian cancer have improved only incrementally. Nanotechnologies designed to locally interrogate and modulate the tumor microenvironment offer a promising opportunity to enhance existing treatment modalities and establish new therapeutic paradigms. By virtue of their elemental composition, geometry, and surface chemistry, nanomaterials can be engineered with optical and pharmacokinetic properties which permit these agents to localize, fluoresce, and deposit energy within tumors. Nanomaterials therefore provide a clear route towards future approaches for sensitive diagnosis and imaging of tumors and targeted therapeutic delivery

Pharmacological interventions in heat stress based on an animal model

Master'sMASTER OF SCIENC

Heating technology for malignant tumors: a review

The therapeutic application of heat is very effective in cancer treatment. Both hyperthermia, i.e., heating to 39-45 degrees C to induce sensitization to radiotherapy and chemotherapy, and thermal ablation, where temperatures beyond 50 degrees C destroy tumor cells directly are frequently applied in the clinic. Achievement of an effective treatment requires high quality heating equipment, precise thermal dosimetry, and adequate quality assurance. Several types of devices, antennas and heating or power delivery systems have been proposed and developed in recent decades. These vary considerably in technique, heating depth, ability to focus, and in the size of the heating focus. Clinically used heating techniques involve electromagnetic and ultrasonic heating, hyperthermic perfusion and conductive heating. Depending on clinical objectives and available technology, thermal therapies can be subdivided into three broad categories: local, locoregional, or whole body heating. Clinically used local heating techniques include interstitial hyperthermia and ablation, high intensity focused ultrasound (HIFU), scanned focused ultrasound (SFUS), electroporation, nanoparticle heating, intraluminal heating and superficial heating. Locoregional heating techniques include phased array systems, capacitive systems and isolated perfusion. Whole body techniques focus on prevention of heat loss supplemented with energy deposition in the body, e.g., by infrared radiation. This review presents an overview of clinical hyperthermia and ablation devices used for local, locoregional, and whole body therapy. Proven and experimental clinical applications of thermal ablation and hyperthermia are listed. Methods for temperature measurement and the role of treatment planning to control treatments are discussed briefly, as well as future perspectives for heating technology for the treatment of tumors

Aerospace medicine and Biology: A continuing bibliography with indexes, supplement 177

This bibliography lists 112 reports, articles, and other documents introduced into the NASA scientific and technical information system in January 1978

Magnetic Hyperthermia for the Treatment of Glioblastoma

Introduction: Glioblastoma, the most common primary adult brain malignancy, is an aggressive tumour with median survival of around one year. Despite extensive research there has been minimal improvement in prognosis and innovative new treatments are urgently required. The research within this thesis focussed on designing a novel therapeutic approach using nanotechnology to achieve in-situ immune stimulation mediated by localised hyperthermia and characterising the effects of hyperthermia within the tumour microenvironment (TME). Methods: In-situ heating was generated using superparamagnetic iron-oxide nanoparticles (SPIONs) stimulated by an alternating magnetic field (AMF); a combined process known as magnetic hyperthermia. Candidate SPIONs were first tested for biocompatibility and favourable heating properties. In-vivo experiments utilised the immunocompetent GL261 glioblastoma model and included: (i) Testing reticuloendothelial system blocking, and direct intratumoural injection to obtain sufficient intratumoural SPION concentrations; (ii) Utilising 89Zr-labelled SPIONs to evaluate in-vivo fate using PET-CT Imaging; (iii) Evaluation of SPION in-vivo heating ability using thermal imaging; (iv) Tumour growth and timed immunohistochemical (IHC) response analysis; (v) Flow cytometry analysis of the tumour infiltrating lymphocyte (TIL) populations following treatment and (vi) testing a combination therapeutic approach combining magnetic hyperthermia with immune checkpoint inhibition. Results: Perimag-COOH was identified as the lead candidate SPION, and intratumoural injection chosen as the optimal method to obtain sufficient intratumoural SPION concentrations. Perimag-COOH remained within the tumour following injection and retained ability to generate AMF-induced heat for at least 72 h post injection. Digital image analysis of IHC demonstrated a specific, localised, heat-shock protein response following hyperthermia. Tumour growth inhibition was observed up to one week following treatment and tumour flow cytometry analysis revealed changes in TIL populations suggestive of an immune response, providing a rational for a combination approach with immune checkpoint inhibition. Conclusions: SPION mediated hyperthermia is achievable in-vivo and can generate TME changes suggestive of an anti-tumour immune response

Elevation in Body Temperature to Fever Range Enhances and Prolongs Subsequent Responsiveness of Macrophages to Endotoxin Challenge

Macrophages are often considered the sentries in innate immunity, sounding early immunological alarms, a function which speeds the response to infection. Compared to the large volume of studies on regulation of macrophage function by pathogens or cytokines, relatively little attention has been devoted to the role of physical parameters such as temperature. Given that temperature is elevated during fever, a long-recognized cardinal feature of inflammation, it is possible that macrophage function is responsive to thermal signals. To explore this idea, we used LPS to model an aseptic endotoxin-induced inflammatory response in BALB/c mice and found that raising mouse body temperature by mild external heat treatment significantly enhances subsequent LPS-induced release of TNF-α into the peritoneal fluid. It also reprograms macrophages, resulting in sustained subsequent responsiveness to LPS, i.e., this treatment reduces “endotoxin tolerance” in vitro and in vivo. At the molecular level, elevating body temperature of mice results in a increase in LPS-induced downstream signaling including enhanced phosphorylation of IKK and IκB, NF-κB nuclear translocation and binding to the TNF-α promoter in macrophages upon secondary stimulation. Mild heat treatment also induces expression of HSP70 and use of HSP70 inhibitors (KNK437 or Pifithrin-µ) largely abrogates the ability of the thermal treatment to enhance TNF-α, suggesting that the induction of HSP70 is important for mediation of thermal effects on macrophage function. Collectively, these results support the idea that there has been integration between the evolution of body temperature regulation and macrophage function that could help to explain the known survival benefits of fever in organisms following infection

Brain hypothermia in ischemic stroke: non-invasive thermometry and molecular basis

Ischemic stroke is a leading cause of death and morbidity around the world. However, only one pharmacological treatment is currently available, the tissue plasminogen activator or rtPA. Preclinical studies demonstrated the high therapeutic potential of hypothermia to mitigate the effects of stroke, but this therapy has not been successfully translated to the clinics due to the side effects associated to cold (shivering, arrhythmia, or pneumonia among others), and due to the lack of non-invasive methods to assess brain temperature. The present work provides new data about the therapeutic potential of focal brain hypothermia as alternative to systemic cooling, the use of non-invasive magnetic resonance thermometry to measure brain temperature, and the possible implication of RBM3, a cold shock protein, in the molecular process underlying the protective effect of cold