Pillar[5]arene-Modified Gold Nanorods as Nanocarriers for Multi-Modal Imaging-Guided Synergistic Photodynamic-Photothermal Therapy

Supramolecular approaches have opened up vast possibilities in the construction of versatile functional materials, especially those with stimuli-responsiveness and integrated functionalities of multi-modal diagnosis and synergistic therapeutics. In this study, a hybrid theranostic nanosystem named TTPY-PyÌCP5@AuNR is constructed via facile host-guest interactions, where TTPY-Py is a photosensitizer with aggregation-induced emission and CP5@AuNR represents the carboxylatopillar[5]arene (CP5)-modified Au nanorods. TTPY-PyÌCP5@AuNR integrates the respective advantages of TTPY-Py and CP5@AuNR such as the high performance of reactive oxygen species (ROS) generation and photothermal conversion, and meanwhile shows fluorescence responses to both temperature and pH stimuli due to the non-covalent interactions. The successful modification of CP5 macrocycles on AuNRs surfaces can eliminate the cytotoxicity of AuNRs and enable them to serve as the nanocarrier of TTPY-Py for further theranostic application. Significantly, both in vitro and in vivo evaluations demonstrate that this supramolecular nanotheranostic system possesses multiple phototheranostic modalities including intensive fluorescence imaging (FLI), photoacoustic imaging (PAI), efficient photodynamic therapy (PDT), and photothermal therapy (PTT), indicating its great potentials for FLI-PAI imaging-guided synergistic PDT-PTT therapy. Besides, TTPY-Py can be released from the nanocarriers upon activating by the acidic environment of lysosomes and then specifically light up mitochondria. This study brings up a new strategy into the design of versatile nanotheranostics for accurate tumor imaging and cancer therapies.