TME-activatable theranostic nanoplatform with ATP burning capability for tumor sensitization and synergistic therapy

Adenosine triphosphate (ATP), as a key substance for regulating tumor progression in the tumor microenvironemnt (TME), is an emerging target for tumor theranostics. Herein, we report a minimalist but versatile nanoplatform with simultaneously TME-responsive drug release, TME-enhanced imaging, ATP-depletion sensitized chemotherapy and photothermal therapy for intelligent tumor theranostics. Methods: The Fe³⁺ and tannic acid (TA) coordination were self-deposited on doxorubicin (Dox) in a facile method to prepare Dox-encapsulated nanoparticles (DFTNPs). Results: When irradiated by a near infrared laser, the DFTNPs could elevate the temperature in the tumor region efficiently. Subsequently, the Dox could be released by the disassembly of Fe³⁺/TA in the TME to initiate chemotherapy. Particularly, the smart nanoagent not only enabled ATP-depletion and enhanced the therapeutic effect of chemotherapy, but also acted as photothermal transduction agent for photothermal therapy. Moreover, the nanoagent also acted as T₁-weighted MR imaging,photoacoustic imaging and photothermal imaging contrast agent. The mice treated by DFTNPs plus laser showed a complete tumor eradication in 14d observation. Conclusion: This as-prepared versatile nanoplatform offers new insights toward the application of smart nanoagents for improved tumor theranostics.