PL–W₁₈O₄₉–TPZ Nanoparticles for Simultaneous Hypoxia-Activated Chemotherapy and Photothermal Therapy

The combination of W 18 O 49 and tirapazamine (TPZ) core has been first introduced into the preparation of poly(ε-caprolactone)–poly(ethylene glycol) (PL) surrounded nanoparticles (NPs). The aim of using W 18 O 49 is employing its capability of reacting with the absorbed O 2 to generate reactive oxygen species (ROS) when exposed to a long-wavelength laser at 808 nm to increase skin penetration and body tolerance. In this work, we have demonstrated that W 18 O 49 unit gives rise to more hypoxic tumor microenvironment and activates the prodrug TPZ to achieve hypoxia-activated chemotherapy, which could be monitored by the intracellular ROS/hypoxia detection and in vivo positron emission tomography imaging. In addition, the successful introduction of W 18 O 49 into PL–W 18 O 49 –TPZ NPs could render the photothermal therapy under the irradiation of an 808 nm laser. As a result, in vivo antitumor results have clearly shown that PL–W 18 O 49 –TPZ NPs could efficiently erase the solid tumor tissues by means of simultaneous hypoxia-activated chemotherapy and photothermal therapy. In comparison to the costly small-molecule photosensitizer chlorine e6 used in hypoxia-activated chemotherapy, W 18 O 49 NPs have two advantages of large-scale preparation and additional photothermal therapy effect, which could provide new insight into future clinical applications.