Ultrafine Titanium Monoxide (TiO_1+x) Nanorods for Enhanced Sonodynamic Therapy

Abstract

Ultrasound (US)-triggered sonodynamic therapy (SDT) that enables noninvasive treatment of large internal tumors has attracted widespread interest. For improvement in the therapeutic responses to SDT, more effective and stable sonosensitizers are still required. Herein, ultrafine titanium monoxide nanorods (TiO1+x NRs) with greatly improved sono-sensitization and Fenton-like catalytic activity were fabricated and used for enhanced SDT. TiO1+x NRs with an ultrafine rodlike structure were successfully prepared and then modified with polyethylene glycol (PEG). Compared to the conventional sonosensitizer, TiO2 nanoparticles, the PEG–TiO1+x NRs resulted in much more efficient US-induced generation of reactive oxygen species (ROS) because of the oxygen-deficient structure of TiO1+x NR, which predominantly serves as the charge trap to limit the recombination of US-triggered electron–hole pairs. Interestingly, PEG–TiO1+x NRs also exhibit horseradish-peroxidase-like nanozyme activity and can produce hydroxyl radicals (•OH) from endogenous H2O2 in the tumor to enable chemodynamic therapy (CDT). Because of their efficient passive retention in tumors post intravenous injection, PEG–TiO1+x NRs can be used as a sonosensitizer and CDT agent for highly effective tumor ablation under US treatment. In addition, no significant long-term toxicity of PEG–TiO1+x NRs was found for the treated mice. This work highlights a new type of titanium-based nanostructure with great performance for tumor SDT.

Recent Advances in Nanomaterial‐Assisted Combinational Sonodynamic Cancer Therapy

“…In another study, Liu's group put forward a new idea on synergistic SDT and CDT cancer treatment by developing novel PEG-TiO 1+x NRs as nanosensitizers for SDT ( Figure 18A). [57] Different from conventional TiO 2 nanoparticles, PEG-TiO 1+x NRs could also be used as Figure 16. A) Schematic presentation of BSO-TCPP-Fe@CaCO 3 -PEG for effective cancer treatment via triple amplification of tumor oxidative stress.…”

“…[ 25c ] Just recently, Liu's group first developed oxygen deficient structural ultrafine titanium monoxide nanorods (TiO 1+ x NRs) with a reduced bandgap than that of TiO 2 for enhanced SDT (Figure 6F). [ 57 ]…”

“…In another study, Liu's group put forward a new idea on synergistic SDT and CDT cancer treatment by developing novel PEG‐TiO 1+ x NRs as nanosensitizers for SDT ( Figure A). [ 57 ] Different from conventional TiO 2 nanoparticles, PEG‐TiO 1+ x NRs could also be used as Fenton‐like agents due to the presence of Ti 3+ , which can decompose the overexpressed H 2 O 2 into highly cytotoxic •OH for CDT‐induced apoptosis. They explored the generated •OH in a Fenton‐like reaction in vitro using o‐phenylenediamine (OPDA) and 3,3′,5,5′‐tetramethylbenzidine (TMB) probes.…”

Recent advances in nanomaterials for sonodynamic therapy

“…In 2020, Wang et al prepared PEG modified ultrafine Ti nanorods (PEG-TiO1+x NRs) which have greatly improved sonosensitization and Fenton-like catalytic activity [122]. The oxygen deficient structure in TiO1+x NRs can be used as the charge trap to inhibit the recombination of (e − ) and (h + ) pairs, resulting a higher ROS generation yield as compared to the traditional TiO2 sonosensitizer.…”

“…Schematic diagram of ultrafine TiO1+x NRs used as a novel sonosensitizer for SDT/CDT of cancer (reproduced with permission from Ref [122],. © American Chemical Society 2020).…”