Targetable Phosphorescent Oxygen Nanosensors for the Assessment of Tumor Mitochondrial Dysfunction By Monitoring the Respiratory Activity†
This work was financially supported by the NSFC (Grants 61078069 and 11274038), the NCET (12-0771), the NSF for Distinguished Young Scholars (61125505), and the FRFCU (2010JBZ006).
Graphical Abstract
Three phosphorescent oxygen nanosensors with specifically modified surface are targetable for extracellular, intracellular, and intramitochondrial O2. The cell respiration is studied with a time-resolved fluorescence microplate reader and expressed in terms of the O2 consumption rates and (intra)cellular O2 gradients. Thereby, the status of the mitochondrial function can be accurately assessed.
Abstract
Cellular respiration is a worthwhile criterion to evaluate mitochondrial dysfunction by measuring the dissolved oxygen. However, most of the existing sensing strategies merely report extracellular (ec-) or intracellular (ic-) O2 rather than intramitochondrial (im-) O2. Herein we present a method to assess tumor mitochondrial dysfunction with three phosphorescent nanosensors, which respond to ec-, ic-, and im-O2. Time-resolved luminescence is applied to determine the respective oxygen consumption rates (OCRs) under varying respiratory conditions. Data obtained for the OCRs and on (intra)cellular O2 gradients demonstrate that mitochondria in tumor cells are distinctly less active than those of healthy cells, resulting from restrained glucose utilization of and physical injury to the mitochondria. We believe that such a site-resolved sensing strategy can be applied to numerous other situations, for example to evaluate the adverse effects of drug candidates.
