Banoxantrone Coordinated Metal−Organic Framework for Photoacoustic Imaging‐Guided High Intensity Focused Ultrasound Therapy

Photoacoustic (PA) imaging with high spatial resolution has great potential as desired monitoring means in the high‐intensity focused ultrasound (HIFU) surgery of tumor. However, its penetration depth in the tissue is insufficient for achieving accurate intraoperative navigation, leading to residual tumor tissue. Nanomedicine provides a new opportunity for PA imaging to guide HIFU surgery. Studies have found that the hypoxic heterogeneity of tumor is effectively reversed by HIFU. Herein, a specific metal−organic framework nanosystem, constructed by coordination of banoxantrone (AQ4N) and Mn2+, is designed based on HIFU to reverse the hypoxic heterogeneity of tumors. It can provide exogenous light‐absorbing substances, thus improving the penetrability of PA imaging signal through the deep tissue and achieving clearer PA imaging for guiding HIFU surgery. In turn, AQ4N, in the hypoxic homogenous environment of the tumor provided by HIFU, is activated sequentially to specifically treat the residual hypoxic tumor cells. This combination treatment manifests higher tumor suppressors activation and lower expression of genes related to tumor progression. This strategy addresses the dissatisfaction with PA imaging‐guided HIFU therapy and is promising for translation into a clinical combination regimen. A specific AQ4N/Mn2+metal−organic framework (AMMOFs) with synergistic properties is developed. The AMMOFs could efficiently provide exogenous light‐absorbing substances for PA imaging‐guided HIFU. Meanwhile, AQ4N is activated sequentially under tumor hypoxic heterogeneity reversed by HIFU and effectively eliminates postoperative residual tissues. This synergy strategy has demonstrated high antitumor properties and PA capabilities both in vitro and in vivo.