The integration of photothermal therapy (PTT) with gene therapy (GT) in a single nanoscale platform demonstrates great potential in cancer therapy. Porous iron oxide nanoagents (PIONs) are widely used as magnetic nanoagents in the drug delivery field and also serve as a photothermal nanoagent for photothermal therapy. However, the therapeutic efficacy of PIONs-mediated GT has not been studied. The long noncoding RNA (lncRNA) CRYBG3 (LNC CRYBG3), a lncRNA induced by heavy ion irradiation in lung cancer cells, has been reported to directly bind to globular actin (G-actin) and cause degradation of cytoskeleton and blocking of cytokinesis, thus indicating its potential for use in GT by simulating the effect of heavy ion irradiation and functioning as an antitumor drug. In the present study, we investigated the possibility of combining PIONs-mediated PTT and LNC CRYBG3-mediated GT to destroy non-small cell lung cancer (NSCLC) cells both in vitro and in vivo. The combination therapy showed a high cancer cell killing efficacy, and the cure rate was better than that achieved using PTT or GT alone. Moreover, as a type of magnetic nanoagent, PIONs can be used for magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) both in vitro and in vivo. These findings indicate that the new combination therapy has high potential for cancer treatment.

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