Hollow MnFe Bimetallic Nanoboxes for Photo/Chemodynamic Therapy via Amplification of Endoplasmic Reticulum Stress

Endoplasmic reticulum stress (ERS) triggered by reactive oxygen species (ROS) buildup can lead to immunogenic cell death (ICD), thereby improving the efficacy of cancer therapy. However, the therapeutic efficacy of this strategy remains limited by the insufficient ROS generation rates of nanomedicines and by the high expression of antioxidants within the tumor microenvironment (TME), which suppresses oxidative stress amplification. Herein, we synthesized Mn/Fe bimetallic Prussian blue analog (PBA) nanoboxes (BMNs) via a facile sodium citrate-assisted method that enables template-free formation of hollow structures, which were loaded with indocyanine green (ICG) to form BMN@ICG for lung cancer treatment. In the acidic TME, BMN@ICG synergistically catalyzes Fenton reactions, while ICG, upon near-infrared irradiation, further amplifies ROS accumulation, thereby enhancing ERS and promoting ICD-mediated apoptosis. This platform significantly improved photo/chemodynamic therapy (CDT) efficacy in lung cancer cells both in vitro and in vivo. This one-step, chelator-driven synthesis offers a scalable route to hollow PBA nanocarriers, suggesting broad potential for multiagent delivery and clinical translation.