Nanohybrids have gained immense popularity for the diagnosis and chemotherapy of lung cancer for their excellent biocompatibility, biodegradability, and targeting ability. However, most of them suffer from limited imaging information, low tumor-to-background ratios, and multidrug resistance, limiting their potential clinical application. Herein, we engineered a photoresponsive nanohybrid by assembling polypyrrole@bovine serum albumin (PPy@BSA) encapsulating perfluoropentane (PFP)/129Xe for selective magnetic resonance (MR)/ultrasonic (US)/photoacoustic (PA) trimodal imaging and photothermal therapy of lung cancer, overcoming these drawbacks of single imaging modality and chemotherapy. The nanohybrid exhibited superior US, PA, and MR multimodal imaging performance for lung cancer detection. The high sensitivity of the nanohybrid to near-infrared light (NIR) resulted in a rapid increase in temperature in a low-intensity laser state, which initiated the phase transition of liquid PFP into the gas. The ultrasound signal inside the tumor, which is almost zero initially, is dramatically increased. Beyond this, it led to the complete depression of 19F/129Xe Hyper-CEST (chemical exchange saturation transfer) MRI during laser irradiation, which can precisely locate lung cancer. In vitro and in vivo results of the nanohybrid exhibited a successful therapeutic effect on lung cancer. Under the guidance of imaging results, a sound effect of photothermal therapy (PTT) for lung cancer was achieved. We expect this nanohybrid and photosensitive behavior will be helpful as fundamental tools to decipher lung cancer in an earlier stage through trimodality imaging methods.

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