An Oxidation-Enhanced Magnetic Resonance Imaging Probe for Visual and Specific Detection of Singlet Oxygen Generated in Photodynamic Cancer Therapy In Vivo

Abstract

Singlet oxygen is regarded as the primary cytotoxic agent in cancer photodynamic therapy (PDT). Despite the advances in optical methods to image singlet oxygen, it remains a challenge for in vivo application due to the limited tissue penetration depth of light. Up to date, no singlet oxygen-specific magnetic resonance imaging (MRI) probe has been reported. Herein, a T₂ -weighted MRI probe is reported to visually detect singlet oxygen generated in PDT in vitro and in vivo. The MRI probe Ce6/Fe₃ O₄ -M is constructed by co-encapsulation of photosensitizer Ce6 and Fe₃ O₄ nanoparticles in mPEG₂₀₀₀ -TK-C₁₆ micelles. Thioketal (TK) linker in the probe is highly sensitive to singlet oxygen, but lowly sensitive to other reactive oxygen species (ROS) existing in physiological and pathological environments. Singlet oxygen, generated with light irradiation, triggers the cleavage of TK, which leads to loss of surface polyethylene glycol, increment of the hydrophobicity, and aggregation of Fe₃ O₄ nanoparticles. Subsequently, negatively enhanced T₂ -weighted MRI signal is obtained for visual detection of singlet oxygen in the solution, cancer cells, and in vivo. This oxidation responsive MRI probe is expected to hold great promise in evaluating the ability of photosensitizers to generate singlet oxygen and in predicting the therapeutic efficacies of PDT in vivo.

Keywords: magnetic resonance imaging; oxidation-responsive micelles; photodynamic therapy; probes; singlet oxygen.