Ultrasound (US) can activate sonosensitizers for sonodynamic therapy (SDT), but the low activation efficiency and therapeutic outcome significantly hinder its further clinical translation. Inspired by the principles of semiconductor physics and photocatalysis chemistry, we herein report on augmenting the sonocatalytic efficiency of semiconductor TiO2-based nanosonosensitizers for highly efficient SDT by the integration of two-dimensional (2D) ultrathin graphene with TiO2 nanosonosensitizers. The high electroconductivity of graphene facilitates the separation of the electron (e-) and hole (h+) pairs from the energy band of TiO2 and avoids their recombination upon external US irradiation; thus it significantly augments the therapeutic efficiency of TiO2 nanosonosensitizers for SDT against tumors. By further MnOx functionalization, these 2D composite nanosonosensitizers achieved tumor microenvironment-sensitive (mild acidity) T1-weighted magnetic resonance imaging of tumors for therapeutic guidance and monitoring. The high photothermal-conversion capability of graphene also synergistically enhanced the SDT efficiency, achieving the complete eradication of a tumor without reoccurrence. This work provides a paradigm for augmenting semiconductor TiO2-based sonocatalytic therapeutic nanomedicine by learning the physiochemical principles from traditional photocatalysis, which also demonstrates a highly efficient noninvasive and safe therapeutic modality for tumor eradication by the nanosonosensitized sonocatalytic process.
Keywords: TiO2 sonosensitizer; graphene; nanomedicine; sonodynamic therapy; synergistic therapy.