Mitochondria-targeted zirconium metal-organic frameworks for enhancing the efficacy of microwave thermal therapy against tumors.

Although microwave (MW) thermal therapy has been widely studied for the treatment of tumors due to its less invasiveness, recurrence of tumors is still observed because of the relatively low bioavailability of MW sensitizers. For enhancing the bioavailability of MW sensitizers, triphenyl phosphate (TPP)-conjugated and doxorubicin (DOX)-loaded porous zirconium metal-organic framework nanocubes (ZrMOF NCs) modified with polyethylene glycol (PEG), ZrMOF-PEG-TPP@DOX NCs, were prepared as a MW sensitizer with mitochondrial-targeting ability. Moreover, the mitochondria are more susceptible to heat than the tumor tissues; this leads to improved tumor cell apoptosis. The results of this study indicate that ZrMOF NCs exhibit excellent heating effects due to the increased collisions of ions in the micropores of ZrMOFs under MW irradiation. In addition, ZrMOF-PEG-TPP@DOX NCs show preferential aggregation in the mitochondria, confirmed by confocal microscopy images. In vivo MW thermal therapeutic efficacy of ZrMOF-PEG-TPP@DOX NCs + MW is also better without recurrence during treatment than that of ZrMOF-PEG@DOX NCs + MW at a similar thermal therapeutic temperature; this reveals that the mitochondrial-targeting strategy can enhance the MW thermal therapeutic efficacy. This study provides a new biosafe MW sensitizer with mitochondrial-targeting ability for enhancing the efficacy of MW thermal therapy against tumors.

Microwave-Activated Mn-Doped Zirconium Metal-Organic Framework Nanocubes for Highly Effective Combination of Microwave Dynamic and Thermal Therapies Against Cancer.

Developing functional nanoagents for achieving the combination of microwave dynamic therapy (MDT) and microwave thermal therapy (MTT) is highly desirable due to the advantages of improving the therapeutic effect on tumors and minimizing the side effects. Metal-organic frameworks (MOFs), as emerging porous materials, exhibit many intriguing properties for application in biomedicine. Herein, new-style flexible Mn-doped zirconium metal-organic framework (Mn-ZrMOF) nanocubes (NCs) with the average size of about 60 nm were prepared easily by a one-pot hydrothermal method. Due to the strong inelastic collision of ions confined in a large number of micropores, the Mn-ZrMOF NCs were demonstrated to be an effective microwave-sensitive agent with a high thermal conversion efficiency up to 28.7%, which is the highest one of the recently reported microwave-sensitive agents. This is the first report of determining the microwave thermal conversion efficiency, which can be used to evaluate, compare, and predict the microwave sensitivity of different microwave-sensitive agents. More importantly, such Mn-ZrMOF NCs generate abundant reactive oxygen species (ROS) of hydroxyl radicals under microwave irradiation. As such, the Mn-ZrMOF NCs efficiently suppress the tumor cell growth in vivo and in vitro under mild microwave irradiation for the synergic effect of MTT and MDT. This work paves the way for developing nanoagents that are responsive to microwave irradiation, producing ROS and improving thermal effects to realize the noninvasive MTT and MDT treatment in clinics.