Abstract Imaging contrast agents are widely investigated in preclinical and clinical studies, among which biogenic imaging contrast agents (BICAs) are developing rapidly and playing an increasingly i Show more
Abstract Imaging contrast agents are widely investigated in preclinical and clinical studies, among which biogenic imaging contrast agents (BICAs) are developing rapidly and playing an increasingly important role in biomedical research ranging from subcellular level to individual level. The unique properties of BICAs, including expression by cells as reporters and specific genetic modification, facilitate various in vitro and in vivo studies, such as quantification of gene expression, observation of protein interactions, visualization of cellular proliferation, monitoring of metabolism, and detection of dysfunctions. Furthermore, in human body, BICAs are remarkably helpful for disease diagnosis when the dysregulation of these agents occurs and can be detected through imaging techniques. There are various BICAs matched with a set of imaging techniques, including fluorescent proteins for fluorescence imaging, gas vesicles for ultrasound imaging, and ferritin for magnetic resonance imaging. In addition, bimodal and multimodal imaging can be realized through combining the functions of different BICAs, which helps overcome the limitations of monomodal imaging. In this review, the focus is on the properties, mechanisms, applications, and future directions of BICAs. Show less
Cancer treatment with platinum compounds is an important achievement of modern chemotherapy. However, despite the beneficial effects, the clinical impact of these agents is hampered by the development Show more
Cancer treatment with platinum compounds is an important achievement of modern chemotherapy. However, despite the beneficial effects, the clinical impact of these agents is hampered by the development of drug resistance as well as dose-limiting side effects. The efficacy but also side effects of platinum complexes can be mediated by uptake through plasma membrane transporters. In the kidneys, plasma membrane transporters are involved in their secretion into the urine. Renal secretion is accomplished by uptake from the blood into the proximal tubules cells, followed by excretion into the urine. The uptake process is mediated mainly by organic cation transporters (OCT), which are expressed in the basolateral domain of the plasma membrane facing the blood. The excretion of platinum into the urine is mediated by exchange with protons via multidrug and toxin extrusion proteins (MATE) expressed in the apical domain of plasma membrane. Recently, the monofunctional, cationic platinum agent phenanthriplatin, which is able to escape common cellular resistance mechanisms, has been synthesized and investigated. In the present study, the interaction of phenanthriplatin with transporters for organic cations has been evaluated. Phenanthriplatin is a high affinity substrate for OCT2, but has a lower apparent affinity for MATEs. The presence of these transporters increased cytotoxicity of phenanthriplatin. Therefore, phenanthriplatin may be especially effective in the treatment of cancers that express OCTs, such as colon cancer cells. However, the interaction of phenanthriplatin with OCTs suggests that its use as chemotherapeutic agent may be complicated by OCT-mediated toxicity. Unlike cisplatin, phenanthriplatin interacts with high specificity with hMATE1 and hMATE2K in addition to hOCT2. This interaction may facilitate its efflux from the cells and thereby decrease overall efficacy and/or toxicity. Show less