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

摘要

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, ox-ox 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.