A pH-responsive NIR fluorescent probe for precise cancer phototheranostics

pH is a key factor of many aspects of daily life and is strongly linked to cancer. Therefore, developing a reliable technique for measuring pH in tumors and looking for novel strategies to enhance tumor treatment efficacy is imperative. A stimulus-responsive phototheranostics platform that integrates imaging and multimodal therapies can effectively improve diagnosis and treatment outcomes. Herein, a pH-responsive and near-infrared (NIR) fluorescent probe featuring Mcl-1 targeting ability was deftly constructed for precise tumor-targeting NIR phototheranostics. The tridentate fluorescent probe , Cy-Nap, was crafted through a comprehensive molecular design strategy that integrated three key components into a single framework. This design included a targeting unit with high affinity for Mcl-1, a NIR-emitting heptamethine cyanine chromophore , and a pH-responsive segment featuring a piperazine ring that serves to link the other two elements within the molecular scaffold . Cy-Nap, an agent designed to be responsive to pH changes, exhibits improved production of reactive oxygen species (ROS) and superior photothermal capabilities under acidic conditions. Additionally, the Cy-Nap probe can be employed to perform intraoperative real-time imaging-guided tumor removal as well as noninvasive, precise NIR imaging of the lymphatic system. Harnessing its tumor-targeting properties, Cy-Nap successfully eliminated tumors in mice with induced tumors when treated with 808 nm laser irradiation , and this was achieved with minimal observable side effects . This work offers novel insights into the development of advanced, multifunctional phototheranostic agents for the therapeutic management of cancer.