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

Abstract

The combination of W18O49 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 W18O49 is employing its capability of reacting with the absorbed O2 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 W18O49 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 W18O49 into PL-W18O49-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-W18O49-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, W18O49 NPs have two advantages of large-scale preparation and additional photothermal therapy effect, which could provide new insight into future clinical applications.