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Hainfeld et al [ 69 ] have recently published a further in vivo study using 1. In this study, a highly radioresistant murine squamous cell carcinoma, SCCVII, was used in mice irradiated with filtered photons produced in a synchrotron.
Using keV photons, significant tumour growth delay and long-term tumour control were observed when 1. This effect was not observed when 30 Gy of radiation was used. Similarly with keV photons, more effect was observed with GNPs combined with There was no analysis of GNP tumour uptake or distribution in this study.
The results of in vivo GNP studies are summarised in Table 2. Nanomedical research remains relatively immature and the full clinical impact is not yet known. Many new nanocomplexes are being developed for cancer therapy and there is a need to translate these products to clinical trials in a timely but safe manner.
It performs and standardises the pre-clinical characterisation of nanomaterials intended for cancer therapeutics.
The NCL will perform physicochemical in vitro and in vivo characterisation and has tested over nanomaterials to date. There was a dramatic improvement in tumour specificity when PEG-thiol was added with active tumour uptake, plateauing at 6 h, and a gradual reduction in liver and spleen concentrations occurred over the same time [ 83 ]. A Phase I study of CYT commenced in , enrolling 29 patients with solid cancers unresponsive to conventional therapies.
Grade II fever, controllable with the use of antipyretics, was the main side effect. The highest dose of TNF used in this trial was more than three times the maximally tolerated dose in historic TNF trials. One partial response and three stable diseases were observed, with further trials in combination with chemotherapy now planned [ 84 ]. Intracellular GNPs were detectable in post-treatment tumour biopsies, but not in normal tissue. Pre-clinical studies of CYT bound with paclitaxel known to synergise with TNF have demonstrated 10 times more paclitaxel uptake in solid tumours than paclitaxel alone [ 81 ].
Patients will receive IV AuroShell particles followed by one or more interstitial illuminations with an nm laser. Post-treatment biopsies will assess nanoparticle uptake in tumours using neutron-activated analysis [ 86 ]. GNPs have many properties that are attractive for use in cancer therapy. They are small and can penetrate widely throughout the body, preferentially accumulating at tumour sites owing to the EPR effect.
Importantly, they can bind many proteins and drugs and can be actively targeted to cancer cells overexpressing cell surface receptors. While they are biocompatible, it is clear that GNP preparations can be toxic in in vitro and in vivo systems.
GNPs have a high atomic number, which leads to greater absorption of kilovoltage X-rays and provides greater contrast than standard agents.
They resonate when exposed to the light of specific energies, producing heat that can be used for tumour-selective photothermal therapy. GNPs have been shown to cause radiosensitisation at kilovoltage and megavoltage photon energies.
The exact mechanism remains to be seen but it may be physical, chemical or biological. Many questions need to be answered before GNP complexes enter routine clinical use.
The factors that affect GNP pharmacokinetics, biodistribution and in vivo toxicity need to be clarified. Targeted GNPs need to exit tumour vasculature, cross the tumour interstitium, enter cells and potentially exit lysosomes to be effective in vivo. They must be able to reach hypoxic cells, which lie far from the vasculature, because these cells are known to be both chemoresistant and radioresistant. Long-term studies are required to evaluate the toxicity and mutagenic potential of GNP RES uptake, because particles may remain in cells for many months.
A standard approach for physicochemical characterisation and pre-clinical testing needs to be implemented, and this process is being aided by the NCL. Rigorous quality assurance needs to ensure minimal batch-to-batch variation, especially when production is scaled up for clinical use. There is huge potential to use nanoparticles in cancer therapy.
With intense global interest in nanotechnology and particularly in nanomedicine, it is likely that many of these questions will be addressed in the near future. National Center for Biotechnology Information , U. Journal List Br J Radiol v.
Br J Radiol. Author information Article notes Copyright and License information Disclaimer. This article has been cited by other articles in PMC. Abstract Gold nanoparticles are emerging as promising agents for cancer therapy and are being investigated as drug carriers, photothermal agents, contrast agents and radiosensitisers. Open in a separate window. Figure 1. Gold nanoparticles as drug carriers There is intense interest in modifying existing drugs to improve pharmacokinetics, thereby reducing non-specific side effects and enabling higher dose delivery to target tissues.
Gold nanoparticle thermal therapy Hyperthermia is known to induce apoptotic cell death in many tissues and has been shown to increase local control and overall survival in combination with radiotherapy and chemotherapy in randomised clinical trials [ 32 - 34 ].
Figure 2. Figure 3. Gold nanoparticles as contrast agents The properties of GNPs, including small size, biocompatibility, high atomic number high-Z and the ability to bind targeting agents, mean that they have potential as contrast agents.
Gold nanoparticles as radiosensitisers While GNP radiosensitisation has been observed in many studies, as discussed below, much work has been phenomenological and the mechanisms by which sensitisation occurs remain unclear. Figure 4. Figure 5. Monte Carlo modelling studies Cho [ 50 ] modelled the effects of GNPs with an iridium source, kilovoltage and megavoltage photon energies.
Table 1 In vitro studies of GNP radiosensitisation with ionising radiation. In vivo studies Despite the rapid increase of GNP publications in recent years and an increasing number of in vivo studies investigating the uptake and distribution of GNPs, there remains a paucity of studies of in vivo radiosensitisation with GNPs.
Figure 6. Figure 7. Table 2 In vivo studies of GNP radiosensitisation with ionising radiation.
Gold nanoparticle clinical trials Nanomedical research remains relatively immature and the full clinical impact is not yet known. Summary GNPs have many properties that are attractive for use in cancer therapy. References 1. West Conshohocken, PA: Toxic potential of materials at the nanolevel. Science ; Service RF. American Chemical Society meeting. Nanomaterials show signs of toxicity. Cellular toxicity of carbon-based nanomaterials.
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Clin Oncol ; Neutrophile Granulozyten sind keine typischen Bestandteile einer periprothetischen Membran [ 3 ]. Morphologische Unterschiede im Aufbau der periprothetischen Membran von zementierten und nicht zementierten Implantaten gibt es nicht, wenngleich bei zementierten Implantaten vermehrt Makrophagen nachgewiesen wurden [ 14 ]. Hinsichtlich der Morphologie der Periimplantatmembran hat sich die Klassifikation von Morawietz et al. Sie besteht aus dicht gepackten Makrophagen, eingebettet in relativ lockeres Bindegewebe.
Neben z. Bei Knieendoprothesen entstehen z. Die Metall-Metall-Gleitpaarung erlebt heute, z.
Meist finden sich staubfeine, an anthrakotisches Pigment erinnernde schwarze bis braunschwarze Ablagerungen. Seltener sind Zirkonoxidkeramiken ZrO2 z. Sie imponieren graubraun bis schwarz, sodass eine Abgrenzung zu metallischem Abrieb schwierig ist. Das Material erscheint im Schnellschnitt glasartig und ist bei schiefer Beleuchtung Kondensor absenken gut sichtbar, zeigt aber keine Doppelbrechung. Der 2.