Nucleic acid-MOF nanoparticle conjugates for NIR/ATP-driven synergetic photo-chemotherapy with hypoxia relief

Herein, a specific kind of nano-platform (ICG-PFH/MOF/DNA-Dox) was developed not only for targeted fluorescence imaging-guided photo-chemotherapy, but also for modulation of hypoxic tumor microenvironment for cancer treatment. Such platform was prepared with metal–organic framework (MOF) as core to serve as matrices for storage of indocyanine green (ICG) and perfluorohexane (PFH), and with double-strand nucleic acids (dsDNA) as shell, which is encoded with both ATP aptamer and AS1411 aptamer as well as used for doxorubicin (Dox) anchoring. Thereout, ICG-PFH/MOF/DNA-Dox reveals active targeting to tumor by recognizing nucleolin receptor sites in cancer cell membranes, following controlled release of Dox in mitochondria due to ATP-triggered dsDNA dissociation to achieve chemotherapy (CT). Under a single laser irradiation, ICG can serve both as photothermal agent to emit heat for photothermal therapy (PTT), and as photosensitizer to generate reactive oxygen species for photodynamic therapy (PDT) of tumors. The loaded PFH acts as O2 self-supplying agent for hypoxia-relieved PDT and CT. Interestingly, the heat from PTT can also help to melt dsDNA to accelerate the Dox release, enhancing CT efficiency. To this end, ICG-PFH/MOF/DNA-Dox shows surprising effect in inhibiting tumor growth both in vitro and in vivo via hypoxia-relieved synergistic PTT/PDT/CT.