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With the advantages of deep tissue penetration and controllability, external X-ray-induced photodynamic therapy (X-PDT) is highly promising for combined cancer therapy. In addition to the low efficiency of photosensitizer (PS) delivery to tumor sites, however, the radiation- and drug-resistance of hypoxic cells inside the tumor after X-PDT also limit its benefits. Herein, we develop a combined therapeutic modality based on an intelligent nanosized platform (DATAT-NPVT) with tumor acidity-activated TAT presenting and redox-boosted release of tirapazamine (TPZ) for more precise and synchronous X-PDT and selective hypoxia-motivated chemotherapy. After DATAT-NPVT has accumulated in tumor tissues via decreased blood clearance by masking of the TAT ligand, its targeting ability is reactivated by tumor pH (∼6.8), which enhances tumoral cellular uptake. Upon low-dose X-ray irradiation, the encapsulated verteporfin (VP) generates reactive oxygen species (ROS) to carry out X-PDT against MDA-MB-231 breast tumors. As a result of the abundant GSH-triggered degradation of ditelluride bridged bonds, the cascaded TPZ release and activation in the hypoxic environment following X-PDT would produce highly cytotoxic radicals to serve as antitumor agents to kill the remaining hypoxic tumor cells. This concept provides new avenues for the design of hierarchical-responsive drug delivery systems and represents a proof-of-concept combinatorial tumor treatment. [ABSTRACT FROM AUTHOR]

Carbon layer-coated molybdenum dioxide nanoparticles exhibit strong photo-absorption in the near infrared (NIR) region with good photostability. The in vitro and in vivo experiments reveal that an excellent photothermal ablation induced from the nanoparticle agents under NIR irradiation can kill tumor cells not only at the cellular level but also in living organs. [ABSTRACT FROM AUTHOR]

Carbon layer-coated molybdenum dioxide nanoparticles exhibit strong photo-absorption in the near infrared (NIR) region with good photostability. The in vitro and in vivo experiments reveal that an excellent photothermal ablation induced from the nanoparticle agents under NIR irradiation can kill tumor cells not only at the cellular level but also in living organs.