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Translational Challenges
Published in Carla Vitorino, Andreia Jorge, Alberto Pais, Nanoparticles for Brain Drug Delivery, 2021
Bárbara Rocha, Nelson Pacheco Rocha, Bruno Gago
The clinical applications of nanoparticles are very significant for early diagnosis and therapy monitoring of disorders such as cancer and neurodegenerative diseases, being an indispensable asset both for the clinician, by aiding in patient management, and for patients, by increasing the odds of survival and quality of life [27]. In fact, nanoparticles are already being used in several bioimaging techniques such as positron emission tomography (PET), magnetic resonance imaging (MRI) and ultrasound (US) [28–30]. In this context, nanoparticles can be used as contrast agents allowing, for instance, the characterisation of early atherosclerotic lesions in the arterial intima of an animal model of the disease [31]. Also, different types of nanoparticles (core-shell structures, matrix-dispersed, self-assembled and micelle-/liposome-like nanoparticles) may be used to detect tumour hypoxia through optical hypoxia imaging [32]. The decrease of pO2 is a common feature of solid tumours and increases with tumour progression. Hence, the possibility to detect hypoxic regions, combining optic hypoxic imaging with more sensitive techniques such as MRI appears to be a powerful tool to detect early-stage cancer [33].
Applications of the Green Fluorescent Protein and Its Variants in Tumor Angiogenesis and Physiology Studies
Published in Mary-Ann Mycek, Brian W. Pogue, Handbook of Biomedical Fluorescence, 2003
Chuan-Yuan Li, Yiting Cao, Mark W. Dewhirst
Besides studying tumor growth and angiogenesis, GFP can also be used to study important problems in tumor physiology. With appropriate genetic manipulation, it is possible to visualize various aspects of important physiological conditions in tumors. For example, tumor hypoxia has long been studied as an important parameter in tumor physiology and therapy. Hypoxia has been identified as a major factor in determining radiation resistance of cancer cells. It has also been suggested as a major factor in tumor angiogenesis since it induces the production of VEGF genes. It has also been reported to be an important prognostic factor for several types of cancer. Therefore, there has been a recent surge of interest in the study of hypoxia in tumors. The use of hypoxia-inducible promoters and the GFP gene makes it possible to visualize hypoxia in tumors noninvasively and thereby provide an approach to study it in greater details in combination with other aspects of tumor development. Koshikawa created a transgenic tumor cell line in which the VEGF promoter is used to control the GFP gene. Up-regulation of GFP is observed under hypoxic condition [43]. Data from our group indicated that it is possible to visualize hypoxia in the dorsal skin window chamber by use of cells that have been artificially transduced with a reporter construct where the GFP gene is under the control of an enhanced hypoxia-responsive promoter (Fig. 2A). In addition, it is possible to visualize activation of another promoter, hsp70 promotor for the heat-shock protein 70 gene (Fig. 2B), whose activation can indicate a variety of stress signals such as heat, glucose deprivation, presence of extra free radicals, and hypoxia [44].
Radiobiology and Hadron Therapy
Published in Manjit Dosanjh, Jacques Bernier, Advances in Particle Therapy, 2018
Eleanor A. Blakely, Manjit Dosanjh
Tumour hypoxia, especially among its cancer stem cells (CSCs), is long associated with radioresistance, and heavy charged-particle therapy is recognised as one of the key therapeutic approaches to treat such radioresistance regardless of the oxygen levels inherent in the heterogeneous tumour micro-environment. The mechanisms underlying hypoxic radioresistance are complex, but several unique molecular mechanisms of action have been uncovered for carbon-ion irradiations compared to photons as noted by Wozny et al. (2017).
The role of N,N-chelate ligand on the reactivity of (η6-p-cymene)Ru(II) complexes: kinetics, DNA and protein interaction studies
Published in Journal of Coordination Chemistry, 2019
Gershom Kyalo Mutua, Rajesh Bellam, Deogratius Jaganyi, Allen Mambanda
The substitution reactivity of the aqua complexes Ru1–Ru6 investigated is strongly dependant on the inherent stereo-electronic properties of the coordinated chelating or bridging ligand. The reactivity of the binuclear complexes is also influenced by the intermetallic distance; as the distance increases the reactivity decreases due to reduced global delocalization of charge with the linking bridge between the metal centers. Two geometric isomeric products are formed in the substitution reactions of the binuclear complexes. The mode of activation for the substitution of the aqua ligands from the complexes is associative. On the other hand, the chloro complexes Ru7–Ru11 showed strong intercalative binding with CT-DNA in which they quenched the florescence emission of the EtBr-CT-DNA complex. The binuclear complexes showed a greater binding affinity for both CT-DNA and BSA due to their higher charge and synergetic effect from the bridging ligand. Owing to its planarity and size, Ru8 had the highest binding ability for CT-DNA and BSA. The great affinity of the complexes to bind BSA in its hydrophobic regions opens a possibility for target drug delivery by these Fe(III) shuttling protein to tumor (hypoxia) cells, which are in hyper demand of Fe(III), an ion mimic of these complexes.