Although microwave ablation is widely used in the treatment of
hepatocellular carcinoma, it is only recommended for the
therapy of
cancer with a diameter of 3 cm or less because of the limited heat transmission radius. Mitochondria play an important role in the apoptotic events of
tumor cells. Here, we developed mitochondria-targeting
zirconia (ZrO2) complex nanoparticles (MZCNs) as nanoagents for efficient
cancer therapy by microwave ablation. The MZCNs are composed of ZrO2 nanoparticles encapsulating the microwave-sensitive
ionic liquid (IL) and co-decorated with the mitochondria-targeting molecule of
triphenylphosphonium (TPP), and the
tumor cell-targeting
peptide iRGD. The cell experiment results reveal that the amount of MZCNs accumulated in the
tumor is obviously increased by the synergistically targeted delivery of TPP and
iRGD peptide after administration by
intravenous injection. Besides, the in vitro experiments demonstrate that MZCNs are distributed preferentially in the mitochondria with the assistance of TPP molecules. More importantly, the in vivo experiments in mice administered with MZCNs show that the effective area with a temperature above 42 °C was about 2.8-fold larger than that of the controls due to the targeting effect and better microwave sensitivity of the MZCNs. As such, the
cancer in mice can be eradicated without recurrence, demonstrating the MZCNs as promising nanoagents for efficient
cancer therapy by microwave ablation.