Oxygen Sensing, Hypoxia Tracing and in Vivo Imaging with Functional Metalloprobes for the Early Detection of Non-communicable Diseases

Abstract

Hypoxia has been identified as one of the hallmarks of tumor environments and a prognosis factor in many cancers. The development of ideal chemical probes for imaging and sensing of hypoxia remains elusive. Crucial characteristics would include a measurable response to subtle variations of pO2 in living systems and an ability to accumulate only in the areas of interest (e.g., targeting hypoxia tissues) whilst exhibiting kinetic stabilities in vitro and in vivo. A sensitive probe would comprise platforms for applications in imaging and therapy for non-communicable diseases (NCDs) relying on sensitive detection of pO2. Just a handful of probes for the in vivo imaging of hypoxia [mainly using positron emission tomography (PET)] have reached the clinical research stage. Many chemical compounds, whilst presenting promising in vitro results as oxygen-sensing probes, are facing considerable disadvantages regarding their general application in vivo. The mechanisms of action of many hypoxia tracers have not been entirely rationalized, especially in the case of metallo-probes. An insight into the hypoxia selectivity mechanisms can allow an optimization of current imaging probes candidates and this will be explored hereby. The mechanistic understanding of the modes of action of coordination compounds under oxygen concentration gradients in living cells allows an expansion of the scope of compounds toward in vivo applications which, in turn, would help translate these into clinical applications. We summarize hereby some of the recent research efforts made toward the discovery of new oxygen sensing molecules having a metal-ligand core. We discuss their applications in vitro and/or in vivo, with an appreciation of a plethora of molecular imaging techniques (mainly reliant on nuclear medicine techniques) currently applied in the detection and tracing of hypoxia in the preclinical and clinical setups. The design of imaging/sensing probe for early-stage diagnosis would longer term avoid invasive procedures providing platforms for therapy monitoring in a variety of NCDs and, particularly, in cancers.

Novel Platinum-Porphyrin as Sensing Compound for Efficient Fluorescent and Electrochemical Detection of H2O2

“…Similar observations were reported by other authors [4,37]. In the studied concentration range, the anodic and cathodic response currents of the Pt-Porf-GCE are directly proportional to the H 2 O 2 concentration, as illustrated in Figure 10A,B).…”

“…In the urine of healthy subjects, the creatinine-corrected H 2 O 2 concentration varies in the range 276-1844 µM, regardless of gender [3]. Reduced oxygen levels are developed in cardiac and brain ischemia [4]. Moreover, H 2 O 2 present in blood can interact with Fe 2+ ions contributing to oxidative stress [5].…”

Quantitative Visualization of Hypoxia and Proliferation Gradients Within Histological Tissue Sections

“…While providing a quantitative readout of oxygen concentrations, they are technically demanding to use and also impart poor spatial resolution. Histological staining against exogenously administered markers of hypoxia provide much higher spatial resolution necessary to image hypoxia micro-regional distribution (Mirabello et al, 2018). A common method to quantify hypoxia in stained histological sections is to apply binary thresholding.…”

Tumor Microenvironment-Responsive Nanomaterials as Targeted Delivery Carriers for Photodynamic Anticancer Therapy

“…Hypoxia is the most common phenomenon in a majority of solid tumors, which provides opportunities for tumor-specific diagnosis and treatment triggered by hypoxia-responsive nanomaterials (Vordermark, 2010 ; McKeown, 2014 ). Growing evidence shows that azobenzene derivatives can be reduced to aniline derivatives by various reductases in the hypoxia environment (Mirabello et al, 2018 ). Owing to excellent hypoxia sensitivity, azobenzene derivatives have widely been used to detect hypoxia levels as hypoxia-reactive fluorescent probes as well as deliver drug or genes to hypoxic cancer cells for anticancer therapy (Perche et al, 2014 ; Dong et al, 2020 ).…”