In Situ and Real-Time Multi-Modality Imaging Guided Orderly Triple-Therapy of Tumors with a Multifunctional Nanodrug.

Effective integration of different therapeutic methods is a promising way to improve the overall efficacy of tumor therapy, which needs to be guided by in situ and real-time monitoring of each therapeutic process. Here a multifunctional AuNR@SiO@MnO@DNA prodrugs (ASMD) nanodrug is designed for orderly photothermal therapy (PTT)/chemodynamic therapy (CDT)/gene therapy (GT) triple-therapy of tumors, which can be guided by the in situ and real-time photoacoustic (PA)/magnetic resonance (MR)/fluorescence (FL) multi-modality imaging. The gold nanorod in ASMD can generate a PA signal and perform PTT. The MnO in ASMD can respond to the glutathione inside tumor cells to release Mn, which can generate MR signal and perform CDT by catalyzing the degradation of intracellular HO to generate ·OH. The DNA prodrugs can perform a cascade response in the presence of the released Mn and the intracellular microRNA 21, which can turn on the quenched FL signal and release small-interfering RNA and antisense oligonucleotide to perform GT. Guiding by the in situ and real-time PA/MR/FL multi-modality imaging of each therapeutic process, an orderly PTT/CDT/GT triple-therapy of tumors is established, which provides a significant and promising strategy to develop more efficient and practical therapeutic programs for tumors.