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@SiO₂@MnO₂@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 MnO₂ in ASMD can respond to the glutathione inside tumor cells to release Mn²⁺, which can generate MR signal and perform CDT by catalyzing the degradation of intracellular H₂O₂ to generate ·OH. The DNA prodrugs can perform a cascade response in the presence of the released Mn²⁺ 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.