Near Infrared Luminescent Oxygen Nanosensors with Nanoparticle Matrix Tailored Sensitivity

The development of sensors for noninvasive determination of oxygen levels in live cells and tissues is critical for the understanding of cellular functions, as well as for monitoring the status of disease, such as cancer, and for predicting the efficacy of therapy. We describe such nontoxic, targeted, and ratiometric 30 nm oxygen nanosensors made of polyacrylamide hydrogel, near-infrared (NIR) luminescent dyes, and surface-conjugated tumor-specific peptides. They enabled noninvasive real-time monitoring of oxygen levels in live cancer cells under normal and hypoxic conditions. The required sensitivity, brightness, selectivity, and stability were achieved by tailoring the interaction between the nanomatrix and indicator dyes. The developed nanosensors may become useful for in vivo oxygen measurements.This work was supported by NIH Grant 1R41 CA 130518-01A1. We thank Dr. Mahaveer S. Bhojani for providing us with A549 cells and Dr. Hao Xu and Prof. Martin Philbert for the C6 glioma, MDA-MB-435, and MCF-7 cells. We thank Mr. Chris Edwards at the Microscopy and Image-analysis Laboratory at the University of Michigan for his technical support in confocal imaging. We also thank the Electron Microbeam Analysis Laboratory (EMAL) at the University of Michigan for their technical support in SEM imaging