W-Doped TiO2 Nanorods for Multimode Tumor Eradication in Osteosarcoma Models under Single Ultrasound Irradiation.

Abstract

Sonosensitizers play crucial roles in the controlled production of reactive oxygen species (ROS) under ultrasound (US) irradiation with high tissue-penetration depth for noninvasive solid tumor therapy. It is desirable to fabricate structurally simple yet multifunctional sonosensitizers from ultrafine nanoparticles for ROS-based multimode therapy to overcome monomode limitations such as low ROS production yields and endogenous reductive glutathione (GSH) to ROS-based treatment resistance. We report the facile high-temperature solution synthesis of ultrafine W-doped TiO2 (W-TiO2) nanorods for exploration of their sonodynamic, chemodynamic, and GSH-depleting activities in sonodynamic-chemodynamic combination tumor therapy. We found that W5+ and W6+ ions doped in W-TiO2 nanorods play multiple roles in enhancing their ROS production. First, W doping narrows the band gap from 3.2 to 2.3 eV and introduces oxygen and Ti vacancies for enhancing their sonodynamic performance. Second, W5+ doping endows W-TiO2 nanorods with Fenton-like reaction activity to produce •OH from endogenous H2O2 in the tumor. Third, W6+ ions reduce endogenous GSH to glutathione disulfide (GSSG) and, in turn, form W5+ ions that further enhance their chemodynamic activity, which greatly modifies thae oxidation-reduction tumor microenvironment in the tumor. In vivo experiments display the excellent ability of W-TiO2 nanorods for enhanced tumor eradication in human osteosarcoma models under single US irradiation. Importantly, the ultrafine nanorod morphology facilitates rapid excretion from the body, displaying no significant systemic toxicity. Our work suggests that multivalent metal doping in ultrafine nanomaterials is an effective and simple strategy for the introduction of new functions for ROS-based multimode therapy.

• Authors: Bijiang Geng, Xue Yang, Ping Li, Wenyan Shi, Dengyu Pan, Longxiang Shen
• Journal: ACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 13 Issue 38 Pg. 45325-45334 (Sep 29 2021) ISSN: 1944-8252 [Electronic] United States
• PMID: 34533945 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Radiation-Sensitizing Agents
• titanium dioxide
• Singlet Oxygen
• Hydroxyl Radical
• Titanium
• Glutathione
• Tungsten

Topics

• Animals
• Antineoplastic Agents (chemistry, radiation effects, therapeutic use)
• Bone Neoplasms (drug therapy)
• Cell Line, Tumor
• Female
• Glutathione (metabolism)
• Humans
• Hydroxyl Radical (metabolism)
• Mice, Inbred BALB C
• Nanotubes (chemistry, radiation effects)
• Osteosarcoma (drug therapy)
• Radiation-Sensitizing Agents (chemistry, radiation effects, therapeutic use)
• Singlet Oxygen (metabolism)
• Titanium (chemistry, radiation effects, therapeutic use)
• Tumor Microenvironment (drug effects)
• Tungsten (chemistry, radiation effects, therapeutic use)
• Ultrasonic Therapy
• Ultrasonic Waves
• Mice