High-Security Nanocluster for Switching Photodynamic Combining Photothermal and Acid-Induced Drug Compliance Therapy Guided by Multimodal Active-Targeting Imaging

High-security nanoplatform with enhanced therapy compliance is extremely promising for tumor. Herein, using a simple and high-efficient self-assembly method, a novel active-targeting nanocluster probe, namely, Ag₂S/chlorin e6 (Ce6)/DOX@DSPE-mPEG₂₀₀₀-folate (ACD-FA) is synthesized. Experiments indicate that ACD-FA is capable of specifically labeling tumor and guiding targeting ablation of the tumor via precise positioning from fluorescence and photoacoustic imaging. Importantly, the probe is endowed with a photodynamic “on-off” effect, that is, Ag₂S could effectively quench the fluorescence of chlorin e6 (89.5%) and inhibit release of ¹O₂ (92.7%), which is conducive to avoid unwanted phototoxicity during transhipment in the body, and only after nanocluster endocytosed by tumor cells could release Ce6 to produce ¹O₂. Moreover, ACD-FA also achieves excellent acid-responsive drug release, and exhibits eminent chemo-photothermal and photodynamic effects upon laser irradiation. Compared with single or two treatment combining modalities, ACD-FA could provide the best cancer therapeutic effect with a relatively low dose, because it made the most of combined effect from chemo-photothermal and controlled photodynamic therapy, and significantly improves the drug compliance. Besides, the active-targeting nanocluster notably reduces nonspecific toxicity of both doxorubicin and chlorin e6. Together, this study demonstrates the potency of a newly designed nanocluster for nonradioactive concomitant therapy with precise tumor-targeting capability.