Tumor microenvironment-activated ROS enhancers for effective inhibition of osteosarcoma

Reactive oxygen species (ROS) in the tumor microenvironment (TME) are key factors involved in inhibiting tumor cell proliferation. This study developed a hollow mesoporous silica-Prussian blue (HMSNs-PB) nanozyme delivery platform loaded with metformin (HPB@MET), which enhances ROS levels within tumor cells through peroxidase-like (POD) activity. Moreover, in the acidic microenvironment of tumors, HPB@MET disintegrates, and the released MET causes mitochondrial dysfunction and increased electron leakage, ultimately promoting the abnormal accumulation of ROS in the TME. In vitro experiments demonstrate that HPB@MET achieves peak cellular uptake at 72 h and significantly inhibits tumor cell proliferation through its exceptional ROS-generating capacity. In the K7M2 osteosarcoma model (initial tumor volume 80 mm³), HPB@MET increased the tumor inhibition rate from 55% with HPB to 76.5%, with median survival extended to 57 days, indicating that HPB@MET synergistically suppresses tumor cell proliferation via POD activity and mitochondrial dysfunction, effectively suppressing osteosarcoma progression. These results indicate that this nanozyme-drug delivery platform can synergistically promote ROS generation in the TME, effectively inhibiting OS and providing a key technological approach for the efficient treatment of this disease.