The Construction of a Multifunctional Nanoscale Porous Coordination Network-222 Nanodrug for Imaging-Guided Chemotherapy-Photodynamic Therapy

Nanoscale metal-organic frameworks have great potential in constructing a high-performance anticancer nanodrug delivery system (NDDS) for combining phototherapy and chemotherapy. However, their practical applications are still challenged by a limited antitumor effect and complex component. In this study, we proposed constructing a multifunctional NDDS via simply integrating positron-emitting radionuclide ⁸⁹Zr and chemotherapeutic doxorubicin (DOX) into the porous coordination network-222 (PCN-222) featuring intrinsic photoactivity and good guest accommodation ability. It has been demonstrated that the synthesized DOX@⁸⁹Zr-PCN-222 exhibits good stability, favorable nanoscale dimensions, and excellent biocompatibility. More importantly, the prepared DOX@⁸⁹Zr-PCN-222 can provide bioinformation on the constructed nanoformulation from the living cells to the whole body, able to achieve controlled release of cytotoxin as a response to low pH and reductive glutathione (GSH). The excellent tumor binding ability of DOX@⁸⁹Zr-PCN-222 has been confirmed by both fluorescence and nuclear imaging, particularly in vivo positron-emission tomography over 7 days. As a result, the prepared NDDS has exhibited remarkable anticancer efficacy to suppress tumor growth and prolong the median survival of a murine breast cancer model, highlighting its great potential for tumor chemo-PDT therapy.