Light-free Generation of Singlet Oxygen through Manganese-Thiophene Nanosystems for pH-Responsive Chemiluminescence Imaging and Tumor Therapy

In chemodynamic therapy (CDT), novel chemodynamic reactions are urgently needed to promote the generating efficiency of reactive oxygen species (ROS), and meanwhile the real-time monitoring of ROS is really critical to minimize the toxic side effect of CDT. Herein, we develop a pH-responsive chemiluminescent and chemodynamic system (ultrathin Mn-oxides [MnOx] nanosheet - semiconducting polymer nanoparticles [SPNs]). We, for the first time, discover the capability of ultrathin MnOx nanosheets to generate ¹O₂ under the trigger of acidity. Notably, the ¹O₂ produced by MnOx can substitute light and specifically excite thiophene-based SPNs to emit photons for near-infrared chemiluminescent imaging, which greatly amplifies the generation of ¹O₂. Because of the intrinsic acidity within tumor, MnOx-SPNs realize the activatable chemodynamic therapy for solid tumor. Furthermore, the ratiometric chemiluminescent/fluorescent imaging is able to calibrate the output of ¹O₂ and achieve more accurate real-time and in situ monitoring of ¹O₂ production during therapy. Chemodynamic therapy (CDT) has been widely used for cancer treatment in pre-clinic research. Although numerous manganese-oxide-based CDT systems have been developed, the unknown catalytic activities of CDT agents may impose on the unpredictable therapeutic outcome and severe side effects in vivo. Here, we report a high-efficiency chemodynamic and chemiluminescenct (CL) system that consists of ultrathin MnOx nanosheet and semiconducting polymer nanoparticles (SPNs). This system exhibited the acid-stimulated CL and ¹O₂ generation. Besides, the yield of ¹O₂ can be real-time monitored by ratiometric imaging of CL/fluorescence for imaging-guided CDT of solid tumor. Our system has the potential to evaluate the therapeutic response and provide instant information to avoid inadequate or excessive drug administration and achieve desirable therapeutic outcomes. This work enriches the alternatives for CDT and provides a promising strategy for effective and precise cancer treatment. We develop a novel chemodynamic and pH-responsive chemiluminescent system (ultrathin MnOx-SPNs). Notably, the ¹O₂ produced by MnOx can substitute light irradiation and specifically excite thiophene-based SPNs for chemiluminescent imaging and meanwhile amplify the generation of ¹O₂ for chemodynamic therapy. Furthermore, the ratiometric chemiluminescent/fluorescent imaging can achieve more accurate real-time monitoring of ¹O₂ production during therapy, which provides a promising imaging tool for precise cancer treatment.