A smart Zr/Co porphyrin MOFs-based nanotheranostics: Triggering ROS storm for potentiated tumor therapy

Reactive oxygen species (ROS)-mediated therapy utilizes the slightly acidic environment of tumor microenvironment and the high amount of H 2 O 2 to disrupt the redox balance of tumor cell while minimizing damage to normal cell. However, this strategy was greatly compromised by the powerful antioxidant capacity of tumors and the limited ROS generation rate of bimetallic metal-organic frameworks (BMOFs). In pursuit of innovative strategies for precise diagnosis and effective treatment, a smart nanotheranostics Zr-TCPP(Co)/ICG/PEG/Apt-M (ZTCIPA) based on Zr/Co porphyrin MOFs was designed. Under 808 nm laser irradiation, ZTCIPA demonstrated exceptional photothermal conversion efficiency alongside robust singlet oxygen ( 1 O 2 ) generation, ensuring potent tumor ablation. Meanwhile, the temperature elevation significantly accelerated the Co 2+ mediated catalytic decomposition of H 2 O 2 to generate •OH. Large amounts of •OH and 1 O 2 formed ROS storm effectively damaged mitochondria and further resulted in tumor cell death. Furthermore, ZTCIPA achieved tumor targeted specificity while enabling real-time fluorescence imaging (FLI)/photothermal imaging (PTI) for accurate tracking. The results in vitro and in vivo demonstrated that ZTCIPA could effectively inhibit tumor growth by photothermal amplified ROS storm under 808 nm laser irradiation. Thus, this novel strategy has enormous potential by solving the bottleneck of ROS-mediated therapies.