Self-assembled metallo-supramolecular nanoflowers for NIR/acidic-triggered multidrug release, long-term tumor retention and NIR-II fluorescence imaging-guided photo-chemotherapy

Abstract On-demand delivery of drug to deep tumor tissues with long-term tumor retention has directly influence on therapeutic efficiency and prognosis of patients, which still remains challenge in cancer therapy. Here we introduce metallo-supramolecular nanoflowers through multi-drugs and metal coordination effect for near-infrared (NIR) or acidic-triggered multi-drugs release, long-term accumulation at tumor tissues and NIR-II fluorescence imaging-guided photo-chemotherapy. The nanoflowers (refer to ICG⊃EDOX) are constructed by (−)-epigallocatechin-3-gallate (EGCG), Cu2+ ions, indocyanine green (ICG) and doxorubicin hydrochloride (DOX) through coordination effect, π-π stacking and hydrophobic force. Due to strong intermolecular interaction, the ICG⊃EDOX is superior stable in physiological conditions, while releases DOX/ICG on-demand upon the acidic/NIR laser irradiation. Moreover, ICG⊃EDOX could penetrate deep tumor tissues with ultralong tumor retention (>8 d) by microvesicle (MVs)-mediated intercellular interaction. Irradiated by 808 nm laser, the higher NIR-II fluorescence signal from ICG⊃EDOX in tumors can effectively guide local phototherapy, and the synergistic therapeutic efficiency of nanoflowers with completely elimination of tumors is achieved in comparison with DOX or DOX/ICG treated 4T1-bearing mice. Overall, the excellent therapeutic effect of nanoflowers may hold great promise for the clinic translation.