pH-Responsive metal-organic framework encapsulated gold nanoclusters with modulated release to enhance photodynamic therapy/chemotherapy in breast cancer

Gold nanoclusters (AuNCs) with an ultra-small size, as new inorganic photosensitizers, have been shown to be promising in photodynamic therapy (PDT), but their application has been restricted due to short blood circulation. It is therefore important to develop stimuli-responsive AuNC-based nanoprobes to achieve highly efficient PDT. Here, metal-organic framework (MOF, ZIF-8) encapsulated AuNCs (AuNCs@MOF) were synthesized, and then they were loaded with doxorubicin (DOX) to obtain pH-responsive nanoprobes (AuNCs@MOF-DOX) with modulated release for enhanced PDT/chemotherapy. In an acidic tumor microenvironment, the structure of ZIF-8 collapsed, accelerating the release of the AuNCs and DOX in the tumor cells, and enhancing the performance of PDT/chemotherapy. Under irradiation with a 670 nm laser, a large amount of singlet oxygen was generated, and the release rate of DOX increased to 77.1% at a pH value of 5.5. By single PDT and single chemotherapy, the tumors were only partially inhibited, but they completely disappeared using the combination of PDT and chemotherapy. The prepared pH-responsive AuNCs@MOF-DOX nanoprobes with modulated release showed excellent PDT/chemotherapy performance, and will be important bi-functional nanoprobes for synergistic therapy