Hydrogels and hydrogel-based materials, thanks to their biocompatibility and biodegradability, are widely used as a supporting matrix for embedding various kinds of luminescent probes for biological sensing applications. Here we describe a family of phosphorescent hydrogels, termed Oxygels, which were designed specifically for local sensing of oxygen by means of Cherenkov-Excited Luminescence Imaging (CELI) in and around tumors during application of radiation therapy. Previously, our group has developed soluble phosphorescent probes, known as Oxyphors, and demonstrated their performance in CELI of oxygen. Oxyphors comprise phosphorescent metalloporphyrins encapsulated inside hydrophobic dendrimers, whose periphery is modified with polyethyleneglycol (PEG) residues. The PEG layer creates a hydrophilic jacket around the dendrimer, precluding interactions of the probe with biomacromolecules. As a result, Oxyphors retain stable calibration parameters, enabling quantitative imaging of oxygen in in vivo. However, locally delivered Oxyphors rapidly diffuse away from the injection sites and spread throughout the body, posing challenges to local oxygen quantification as well as raising concerns in terms of regulatory (FDA) approval. To this end, hydrogel-supported phosphorescent sensors implanted into tissue should allow for continuous local monitoring of oxygen during RT, aiding optimization of treatment protocols and facilitating the development of new types of RT treatment.
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