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•Laser-induced breakdown spectroscopy is a major tool for imaging chemical elements in tissues.•Imaging of trace, minor or major elements with LIBS requires minor sample ...preparation.•Both endogenous and exogenous metal elements from the tissues are simultaneously detectable.•Tissue imaging with LIBS has straightforward applications for preclinical and medical studies.
Biological tissues contain various metal and metalloid ions that play different roles in the structure and function of proteins and are therefore indispensable to several vital biochemical processes. In this review, we discuss the broad capability of laser-induced breakdown spectroscopy (LIBS) for in situ elemental profiling and mapping of metals in biological materials such as plant, animal and human specimens. These biological samples contain or accumulate metal species and metal-containing compounds that can be detected, quantified, and imaged. LIBS enables performing microanalysis, mapping and depth profiling of endogenous and exogenous elements contained in the tissues with a parts-per-million scale sensitivity and microscopic resolution. In addition, this technology generally requires minimal sample preparation. Moreover, its tabletop instrumentation is compatible with optical microscopy and most elements from the periodic table. Specifically, low- and high-atomic-number elements can be detected simultaneously. Recent advances in space-resolved LIBS are reviewed with various examples from vegetable, animal and human specimens. Overall, the performance offered by this new technology along with its ease of operation suggest innumerable applications in biology, such as for the preclinical evaluation of metal-based nanoparticles and in medicine, where it could broaden the horizons of medical diagnostics for all pathologies involving metals.
In the human body, copper (Cu) is a major and essential player in a large number of cellular mechanisms and signaling pathways. The involvement of Cu in oxidation-reduction reactions requires close ...regulation of copper metabolism in order to avoid toxic effects. In many types of cancer, variations in copper protein levels have been demonstrated. These variations result in increased concentrations of intratumoral Cu and alterations in the systemic distribution of copper. Such alterations in Cu homeostasis may promote tumor growth or invasiveness or may even confer resistance to treatments. Once characterized, the dysregulated Cu metabolism is pinpointing several promising biomarkers for clinical use with prognostic or predictive capabilities. The altered Cu metabolism in cancer cells and the different responses of tumor cells to Cu are strongly supporting the development of treatments to disrupt, deplete, or increase Cu levels in tumors. The metallic nature of Cu as a chemical element is key for the development of anticancer agents via the synthesis of nanoparticles or copper-based complexes with antineoplastic properties for therapy. Finally, some of these new therapeutic strategies such as chelators or ionophores have shown promising results in a preclinical setting, and others are already in the clinic.
More than 50% of all cancer patients receive radiation therapy. The clinical delivery of curative radiation dose is strictly restricted by the proximal healthy tissues. We propose a dual-targeting ...strategy using vessel-targeted-radiosensitizing gold nanoparticles and conformal-image guided radiation therapy to specifically amplify damage in the tumor neoendothelium. The resulting tumor vascular disruption substantially improved the therapeutic outcome and subsidized the radiation/nanoparticle toxicity, extending its utility to intransigent or nonresectable tumors that barely respond to standard therapies.
A simple NIR-II emitting water-soluble system has been developed and applied in vitro and in vivo. In vitro, the fluorophore quickly accumulated in 2D and 3D cell cultures and rapidly reached the ...tumor in rodents, showing high NIR-II contrast for up to 1 week. This very efficient probe possesses all the qualities necessary for translation to the clinic as well as for the development of NIR-II emitting materials.
Abstract
Zinc (Zn) is a crucial trace element involved in various cellular processes, including oxidative stress, apoptosis and immune response, contributing to cellular homeostasis. Dysregulation of ...Zn homeostasis occurs in certain cancers. This review discusses the role of Zn in cancer and its associated components, such as Zn‐related proteins, their potential as biomarkers and the use of Zn‐based strategies for tumor treatment. ZIP and ZnT proteins regulate Zn metabolism under normal conditions, but their expression is aberrant in cancer. These Zn proteins can serve as prognostic or diagnostic biomarkers, aiding in early cancer detection and disease monitoring. Moreover, targeting Zn and its pathways offers potential therapeutic approaches for cancer treatment. Modulating Zn biodistribution within cells using metal‐binding agents allows for the control of downstream signaling pathways. Direct utilization of zinc as a therapeutic agent, including Zn supplementation or Zn oxide nanoparticle administration, holds promise for improving the prognosis of cancer patients.
IntroductionOccurrence of multiple brain metastases is a critical evolution of many cancers with significant neurological and overall survival consequences, despite new targeted therapy and standard ...whole brain radiotherapy (WBRT). A gadolinium-based nanoparticle, AGuIX, has recently demonstrated its effectiveness as theranostic and radiosensitiser agent in preclinical studies. The favourable toxicity profile in animals and its administration as a simple intravenous injection has motivated its use in patients with this first in human study.Methods and analysisThe NANO-RAD study is a phase I, first in human injection, monocentric, open-label, dose-escalation study to investigate the safety, the tolerability and the spectrum of side effects of AGuIX in combination with WBRT (30 Gy, 10 fractions of 3 Gy) for patients with multiple brain metastases. Five dose escalation cohorts are planned: 15, 30, 50, 75 and 100 mg/kg. A total of 15–18 patients will be recruited into this trial. The primary objective is to determine the maximum-tolerated dose of AGuIX nanoparticles combined with WBRT for the treatment of multiple brain metastases. Toxicity will be assessed using the National Cancer Institute Common Toxicity Criteria V.4.03. Secondary objectives are pharmacokinetic profile, distribution of AGuIX in metastases and surrounding healthy tissue visualised by MRI, intracranial progression-free survival and overall survival. Intracranial response will be determined according to Response Evaluation Criteria in Solid Tumour Criteria V.1.1 comparing MRI performed prior to treatment and at each follow-up visits.Ethics and disseminationApproval was obtained from the ethics committee Sud Est V, France (Reference number 15-CHUG-48). The study was approved by the French National Agency for the Safety of Medicines and Health Products (ANSM) (Reference number 151519A-12). The results will be published in peer-reviewed journals or disseminated through national and international conferences.Trial registration number NCT02820454; Pre-results.
Iron (Fe) is a trace element that plays essential roles in various biological processes such as DNA synthesis and repair, as well as cellular energy production and oxygen transport, and it is ...currently widely recognized that iron homeostasis is dysregulated in many cancers. Indeed, several iron homeostasis proteins may be responsible for malignant tumor initiation, proliferation, and for the metastatic spread of tumors. A large number of studies demonstrated the potential clinical value of utilizing these deregulated proteins as prognostic and/or predictive biomarkers of malignancy and/or response to anticancer treatments. Additionally, the iron present in cancer cells and the importance of iron in ferroptosis cell death signaling pathways prompted the development of therapeutic strategies against advanced stage or resistant cancers. In this review, we select relevant and promising studies in the field of iron metabolism in cancer research and clinical oncology. Besides this, we discuss some co-existing discrepant findings. We also present and discuss the latest lines of research related to targeting iron, or its regulatory pathways, as potential promising anticancer strategies for human therapy. Iron chelators, such as deferoxamine or iron-oxide-based nanoparticles, which are already tested in clinical trials, alone or in combination with chemotherapy, are also reported.
Nanoparticles containing high-Z elements are known to boost the efficacy of radiation therapy. Gadolinium (Gd) is particularly attractive because this element is also a positive contrast agent for ...MRI, which allows for the simultaneous use of imaging to guide the irradiation and to delineate the tumor. In this study, we used the Gd-based nanoparticles, AGuIX®. After intravenous injection into animals bearing B16F10 tumors, some nanoparticles remained inside the tumor cells for more than 24 hours, indicating that a single administration of nanoparticles might be sufficient for several irradiations. Combining AGuIX® with radiation therapy increases tumor cell death, and improves the life spans of animals bearing multiple brain melanoma metastases. These results provide preclinical proof-of-concept for a phase I clinical trial.
Interfacing ultrasmall metal nanoclusters (NCs) with proteins can present a dual opportunity: proteins can be used for protecting NCs, and the surface ligands of NCs may interact with proteins. Here, ...the authors identify and discuss remaining open questions surrounding the bio-NC interface that call for future research efforts.
Three near-infrared (NIR-I) optical theranostic systems were synthesized, characterized and studied in vitro and in vivo. These original homo-bimetallic gold(I)-based aza-BODIPY complexes proved to ...be trackable through near-infrared optical imaging in cells and in mice. They display anti-proliferative properties in micromolar range against human and murine cancer cell lines (4T1, MDA-MB-231, CT26, and SW480). Moreover, the injection of the most promising theranostic agent in CT26 tumor-bearing BALB/c mice induced a significant anti-cancer activity.
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•Design of efficient aza-BODIPY-based homo-bimetallic gold(I) theranostics.•High in vitro anti-proliferative properties (4 < IC50 < 10 μM on 4 cancer cell lines).•Significant anti-cancer effect of aza-BODI-Au-1 in tumor-bearing BALB/c mice.•The compounds can be tracked in vitro and in vivo by NIR-optical imaging.
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