Self-recognizing and stimulus-responsive carrier-free metal-coordinated nanotheranostics for magnetic resonance/photoacoustic/fluorescence imaging-guided synergistic photo-chemotherapy
Carrier-free nanotheranostics directly assembled by clinically used photosensitizers and chemotherapeutic drugs are a promising alternative for tumor theranostic. However, the weak interaction-driven assembly still suffers from low structural stability against disintegration, lack of targeting specificity, and poor stimulus-responsive property. Moreover, almost all exogenous ligands possess no therapeutic effect. Enlightened by the concept of metal-organic frameworks, we developed a novel self-recognizing metal-coordinated nanotheranostic agent by coordination-driven co-assembly of photosensitizer indocyanine green (ICG) and chemo-drug methotrexate (MTX, also served as a specific “targeting ligand” towards folate receptors), in which ferric (FeⅢ) ion acted as a bridge to tightly associate ICG with MTX. Such carrier-free metal-coordinated nanotheranostics with high dual-drug payload (~94 wt%) not only possessed excellent structural and physiological stability, but also exhibited prolonged blood circulation. Additionally, the nanotheranostics could achieve targeted on-demand drug release by both stimuli of internal lysosomal acidity and external near-infrared laser. More importantly, the nanotheranostics could self-recognize the cancer cells and selectively target to the tumors, therefore it decreased toxicity to normal tissues and organs. Consequently, the nanotheranostics showed strongly synergistic potency for tumor photo-chemotherapy under the precise guidance of magnetic resonance/photoacoustic/fluorescence imaging, thereby achieving highly effective tumor cure efficiency. Considering that ICG and bi-functional MTX are approved by Food and Drug Administration, and FeⅢ ions have high biosafety, the self-recognizing and stimulus-responsive carrier-free metal-coordinated nanotheranostics may hold potential application in tumor theranostic.