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

Abstract

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

Tumor‐Targeting W18O49 Nanoparticles for Dual‐Modality Imaging and Guided Heat‐Shock‐Response‐Inhibited Photothermal Therapy in Gastric Cancer

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Size and Shape Effects of Near‐Infrared Light‐Activatable Cu2(OH)PO4 Nanostructures on Phototherapeutic Destruction of Drug‐Resistant Hypoxia Tumors

“…In the literature, fluorinated nanoplatforms, PL-W 18 O 49 -TPZ nanoparticles and nano perfluorocarbons (PFC), were reported as anticancer agents to overcome hypoxia. [7][8][9] Despite overcoming hypoxia and Development of simple, robust, and noninvasive therapeutic approaches to treat cancers and improve survival rates is a grand challenge in clinical biomedicine. In particular, the sizes and shape of the nanomaterials play a vital role in dictating their biodistribution and clearance pathways.…”

<p>Combinational phototherapy and hypoxia-activated chemotherapy favoring antitumor immune responses</p>

“…The synthesis procedure of poly(ε-caprolactone)-poly (ethylene glycol) (PEG-PCL) was performed as previously described. 54 PEG-PCL-IR780-TPZ nanoparticles (NPs) were prepared using oil-in-water emulsion solvent diffusion method. 54,55 Briefly, IR780 (2.5 mg) and TPZ (2.5 mg) were dissolved in 10 mL of dichloromethane and PEG-PCL was dissolved in 10 mL of deionized water.…”