Rational design of Multi-model ROS regulation Nano-platform for enhanced Mild-temperature photothermal therapy

The tumor thermotolerance owing to the overexpression of heat shock proteins (HSPs) is the critical challenge in practical application of mild-temperature photothermal therapy (MPTT). Reactive oxygen species (ROS) can not only serve as a powerful weapon to kill cancer cells, but also a regulator to inhibit HSPs, thus improving the thermal sensitivity of tumors. Herein, a multi-model ROS regulation nano-platform based on TCLP nanocomposites consisting of polyacrylic acid encapsulated, chloroperoxidase (CPO) and β-Lapachone (β-Lap) loaded black mesoporous titanium (H-TiO 2 ) has been constructed for the ROS-enhanced MPTT. In this nano-platform, the H-TiO 2 acts as the NIR-Ⅱ light triggered photothermal agent and photosensitizer to contribute to deep tissue MPTT and PDT, the β-Lap acts as a H 2 O 2 amplifier to improve the 1 O 2 production of CPO. The abundant ROS from TCLP NPs can limit the activity as well as the expression of HSPs, ultimately improving the antitumor efficacy of MPTT. Finally, excellent synergistic tumor inhibition based on TCLP NPs has been reached both in vitro and in vivo. This multi- model ROS enhanced MPTT nano-platform with low toxic side effects offers a promising strategy and enlightenments the clinical application of MPTT.