Major determining factors for survival of patients with oral, oropharyngeal, and esophageal cancer are early detection, the quality of surgical margins, and the contemporaneous detection of residual tumor. Intuitively, the exposed location at the epithelial surface qualifies these tumor types for utilization of visual aids to assist in discriminating tumor from healthy surrounding tissue. Here, we explored the DNA repair enzyme PARP1 as imaging biomarker and conducted optical imaging in animal models, human tissues and as part of a first-in-human clinical trial. Our data suggests that PARP1 is a quantitative biomarker for oral, oropharyngeal, and esophageal cancer and can be visualized with PARPi-FL, a fluorescently labeled small molecule contrast agent for topical or intravenous delivery. We show feasibility of PARPi-FL-assisted tumor detection in esophageal cancer, oropharyngeal and oral cancer. We developed a contemporaneous PARPi-FL topical staining protocol for human biospecimens. Using fresh oral cancer tissues within 25 min of biopsy, tumor and margin samples were correctly identified with >95% sensitivity and specificity without terminal processing. PARPi-FL imaging can be integrated into clinical workflows, potentially providing instantaneous assessment of the presence or absence of microscopic disease at the surgical margin. Additionally, we showed first-in-human PARPi-FL imaging in oral cancer. In aggregate, our preclinical and clinical studies have the unifying goal of verifying the clinical value of PARPi-FL-based optical imaging for early detection and intraoperative margin assignment.
The rise of nanotechnology has brought to the world a new potential and broader perspective of what humanity can achieve through material manipulation at the nanoscale. As a consequence, the use of different nanomaterials has revolutionized both the industrial and biomedical worlds. Metallic and metal-oxide nanostructures have shown great potential due to their high surface to volume ratio and high reactivity. Among them, zinc oxide (ZnO) has revealed wider applicability, including in nanomedicine, where ZnO nanomaterials have shown great potential leading to effective interactions with biological membranes and exhibiting antibacterial and/or anticancer behaviors. However, consistent with several other nanostructures, the synthesis of ZnO nanomaterials is not devoid of drawbacks, such as the production of harmful and toxic byproducts, the use of toxic reagents, the employment of expensive instruments, and the lack of biocompatibility, all of which need to be overcome before extensive use. As a solution, green nanotechnology has allowed the production of ZnO nanostructures using environmentally friendly and cost-effective methods, which are based on the use of living organisms, natural biomolecules and waste materials. Once produced, green-synthesized ZnO nanoparticles have shown enhancements in terms of their cytocompatibility and biomedical properties compared to their traditionally produced counterparts, becoming excellent antibacterial or anticancer agents. These ZnO nanoparticles have also proven to be valuable materials in combination with wound healing processes and biosensing elements in order to trace small amounts of biomarkers associated with different diseases. As a consequence, there is a synergy between green nanotechnology and ZnO nanomaterials, which is leading to an exciting flourishment in the field, presenting a wide variety of biomedical applications for these nanostructures. This review compares and contrasts recent approaches and examples of the use of green-synthesized ZnO nanomaterials with traditionally synthesized structures, demonstrating a remarkable potential for their use as a powerful biomedical agent.
Cancer and antimicrobial resistance to antibiotics are two of the most worrying healthcare concerns that humanity is facing nowadays. Some of the most promising solutions for these healthcare problems may come from nanomedicine. While the traditional synthesis of nanomaterials is often accompanied by drawbacks such as high cost or the production of toxic by-products, green nanotechnology has been presented as a suitable solution to overcome such challenges. In this work, an approach for the synthesis of tellurium (Te) nanostructures in aqueous media has been developed using aloe vera (AV) extracts as a unique reducing and capping agent. Te-based nanoparticles (AV-TeNPs), with sizes between 20 and 60 nm, were characterized in terms of physicochemical properties and tested for potential biomedical applications. A significant decay in bacterial growth after 24 h was achieved for both Methicillin-resistant Staphylococcus aureus and multidrug-resistant Escherichia coli at a relative low concentration of 5 µg/mL, while there was no cytotoxicity towards human dermal fibroblasts after 3 days of treatment. AV-TeNPs also showed anticancer properties up to 72 h within a range of concentrations between 5 and 100 µg/mL. Consequently, here, we present a novel and green approach to produce Te-based nanostructures with potential biomedical applications, especially for antibacterial and anticancer applications.
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