A mild and efficient sonothermal tumor therapy enhanced by sonodynamic effect with biodegradable red phosphorus nanoparticles

Due to the shallow penetration depth of light in biological tissues, the effectiveness of photothermal therapy (PTT) in deep-seated tumors is limited. Conversely, ultrasonic wave has excellent tissue penetration depth. Using ultrasound (US) as an exogenous physical stimulus to trigger tumors thermotherapy is a promising alternative for deep-seated tumors to supersede conventional PTT. Here, we realized a mild sonothermal therapy (STT) using biodegradable red phosphorus nanoparticles (RP NPs) as sonothermal agents. Quite obvious sonothermal conversion of RP NPs is remarkable under low intensity US irradiation, with the temperature rise from 30 to 47 °C at tumor site. In terms of potential mechanism, under US excitation, the internal electrons of RP NPs undergo transition and release the energy by electrons and holes recombination process. This elicits the atom thermal vibration and raises the temperature around the RP NPs. Additionally, US irradiation can stimulate RP NPs to produce singlet oxygen (1O2) and reduce intracellular energy levels that leads to downregulation of the heat shock proteins (HSPs) expression, providing an "escort" to mild STT. This work offers a new paradigm for the strategies of STT enhanced by sonodynamic effect.