Multifunctional Composite Nanosystems for Precise/Enhanced Sonodynamic Oxidative Tumor Treatment.

Ultrasound-activated therapies have been regarded as the efficient strategy for tumor treatment, among which sonosensitizer-enabled sonodynamic oxidative tumor therapy features intrinsic advantages as compared to other exogenous trigger-activated dynamic therapies. Nanomedicine-based nanosonosensitizer design has been extensively explored for improving the therapeutic efficacy of sonodynamic therapy (SDT) of tumor. This review focuses on solving two specific issues, i.e., precise and enhanced sonodynamic oxidative tumor treatment, by rationally designing and engineering multifunctional composite nanosonosensitizers. This multifunctional design can augment the therapeutic efficacy of SDT against tumor by either improving the production of reactive oxygen species or inducing the synergistic effect of SDT-based combinatorial therapies. Especially, this multifunctional design is also capable of endowing the nanosonosensitizer with bioimaging functionality, which can effectively guide and monitor the therapeutic procedure of the introduced sonodynamic oxidative tumor treatment. The design principles, underlying material chemistry for constructing multifunctional composite nanosonosensitizers, intrinsic synergistic mechanism, and bioimaging guided/monitored precise SDT are summarized and discussed in detail with the most representative paradigms. Finally, the existing critical issues, available challenges, and potential future developments of this research area are also discussed for promoting the further clinical translations of these multifunctional composite nanosonosensitizers in SDT-based tumor treatment.