Abstract
Simple SummaryTumor hypoxia is a documented negative prognostic factor that contributes to treatment resistance in head and neck cancer. In the present study, we use non-invasive magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) to evaluate the ability of ultra-small manganese dioxide coated nanoparticles to modulate tumor oxygenation in vitro and in vivo. Our results highlight the utility of MRI and PAI in mapping tumor hypoxia and nanoparticle delivery and demonstrate the potential of image-guided nanodelivery in alleviating tumor hypoxia in head and neck cancer.There is widespread interest in developing agents to modify tumor hypoxia in head and neck squamous cell carcinomas (HNSCC). Here, we report on the synthesis, characterization, and potential utility of ultra-small NaYF4:Nd3+/NaGdF4 nanocrystals coated with manganese dioxide (usNP-MnO2) for spatiotemporal modulation of hypoxia in HNSCC. Using a dual modality imaging approach, we first visualized the release of Mn2+ using T1-weighted magnetic resonance imaging (MRI) and modulation of oxygen saturation (%sO2) using photoacoustic imaging (PAI) in vascular channel phantoms. Combined MRI and PAI performed in patient-derived HNSCC xenografts following local and systemic delivery of the hybrid nanoparticles enabled mapping of intratumoral nanoparticle accumulation (based on T1 contrast enhancement) and improvement in tumor oxygenation (increased %sO2) within the tumor microenvironment. Our results demonstrate the potential of hybrid nanoparticles for the modulation of tumor hypoxia in head and neck cancer. Our findings also highlight the potential of combined MRI-PAI for simultaneous mapping nanoparticle delivery and oxygenation changes in tumors. Such imaging methods could be valuable in the precise selection of patients that are likely to benefit from hypoxia-modifying nanotherapies.
Highlights
Head and neck squamous cell carcinomas (HNSCC) are a unique group of neoplasms that exhibit aggressive biological behavior and therapeutic resistance [1]
In the context of imaging hypoxia, studies by us and others have shown that differences in optical absorption characteristics between oxygenated hemoglobin (OxyHb) and deoxygenated hemoglobin can be exploited by Photoacoustic imaging (PAI) to obtain relative estimates of oxygen saturation (%sO2 ) in vivo [12,13,14]
The MnO2 shell has multiple functional capabilities. It reacts with reactive oxygen species (ROS), hydrogen peroxide (H2 O2 ) present within the tumor microenvironment to convert it to
Summary
Head and neck squamous cell carcinomas (HNSCC) are a unique group of neoplasms that exhibit aggressive biological behavior and therapeutic resistance [1]. In this regard, hypoxia is a major cause of therapeutic resistance and a documented negative prognostic factor in HNSCC [2,3,4,5]. There has been widespread interest in developing agents that modify tumor hypoxia (e.g., nitroimidazoles) [6] While these agents offer the potential to enhance therapeutic efficacy (improved local control and survival), results from clinical studies of such agents in unselected patients have been disappointing, due to varying levels of oxygenation during disease progression and therapy [6,7,8].
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