A Single-wavelength NIR-triggered Polymer for in Situ Generation of Peroxynitrite (ONOO−) to Enhance Phototherapeutic Efficacy

Phototherapies including photodynamic therapy (PDT) and photothermal therapy (PTT) are the most promising and non-invasive cancer treatments. However, the efficacy of mono-therapy of PDT or PTT is often limited by the phototherapeutic defects such as low light penetration depth of photosensitizers and insufficiency of photothermal agents. Peroxynitrite (ONOO−) has been proved to be an efficient oxidizing and nitrating agent that involves in various physiological and pathological processes. Therefore, ONOO− produced in tumor site could be an effective treatment in cancer therapy. Herein, a novel cyanine dye-based (Cy7) polymer nanoplatform is developed for enhanced phototherapy by in situ producing ONOO−. The Cy7 units in the nanoparticles can not only be served as the photosensitizer to produce reactive oxygen species (ROS) including singlet oxygen and superoxide anion for PDT, but also be used as a heat source for PTT and the release of NO gas from N-nitrosated napthalimide (NORM) at the same time. Since NO can react quickly with superoxide anion to generate ONOO−, the enhanced phototherapy could be achieved by in situ ONOO− produced by PCy7-NO upon exposure to the near infrared (NIR) light. Therefore, the NIR-triggered Cy7-based nanoplatform for ONOO−-enhanced phototherapy may provide a new perspective in cancer therapy.