Construction of TiO₂@Ag₂O p-n junctions for synergistic sonodynamic/sonothermal tumor therapy with enhanced efficacy

With the deepening of research of sonodynamic therapy (SDT), it is shown that the efficacy of single component and single functional sonosensitizers is not satisfactory. Therefore, this study utilized multihole TiO₂@Ag₂O (TA) as sonosensitizer to achieve synergetic SDT and sonothermal therapy (STT) under US irradiation. As a p-n nanoformulation, the construction of TA is conducive to generate a built-in electric field and lead to energy band bending, which are efficient in separating electrons and holes. Besides, it can promote carrier relaxation between the different energy bands to produce abundant phonons, inducing lattice thermal vibration and realizing the conversion of mechanical energy to thermal energy. Moreover, the feasibility of enhancing cavitation effect for improving sonothermal capability is demonstrated for the first time. When TA enters tumor cells under US irradiation, plentiful •OH and ¹O₂ are generated to attack mitochondria, causing dysfunction, disrupting energy supply and damaging DNA, thereby inducing apoptosis. Meanwhile, TA can also cause rapid local heating of surrounding environment to kill tumor cells by lattice thermal vibration and cavitation bubbles bursting on its surface. Obviously, this work effectively achieves both heterojunction enhanced SDT, and carrier relaxation and cavitation effect promoted STT combined anti-tumor therapy through designing multihole p-n TA. STATEMENT OF SIGNIFICANCE: Sonothermal therapy (STT) is considered a promising alternative to photothermal therapy due to its high penetration, minimal side effects and wide applicability. However, the understanding of the mechanism and influence factors of STT is still in the initial stage, and further research on STT is very necessary for its development. Therefore, our work constructed a porous nano p-n junction that could generate abundant OH and 1O2 and induce local heating under ultrasound irradiation, achieving the combined sonodynamic and sonothermal treatment. Importantly, this study not only proved that appropriate adjustment of carrier relaxation degree could affect the materials sonothermal conversion ability, but also proposed and confirmed for the first time that the enhanced cavitation effect of porous structures can promote the STT effectiveness.