Iron oxide nanoparticles could significantly promote the mitochondrial transfer from mesenchymal stem cells to the injured cells.

The use of exogenous mitochondria to replenish damaged mitochondria has been proposed as a strategy for the treatment of pulmonary fibrosis. However, the success of this strategy is partially restricted by the difficulty of supplying sufficient mitochondria to diseased cells. Herein, we report the generation of high-powered mesenchymal stem cells with promoted mitochondrial biogenesis and facilitated mitochondrial transfer to injured lung cells by the sequential treatment of pioglitazone and iron oxide nanoparticles. This highly efficient mitochondrial transfer is shown to not only restore mitochondrial homeostasis but also reactivate inhibited mitophagy, consequently recovering impaired cellular functions. We perform studies in mouse to show that these high-powered mesenchymal stem cells successfully mitigate fibrotic progression in a progressive fibrosis model, which was further verified in a humanized multicellular lung spheroid model. The present findings provide a potential strategy to overcome the current limitations in mitochondrial replenishment therapy, thereby promoting therapeutic applications for fibrotic intervention.

In recent years, gene therapy has made remarkable achievements in tumor treatment. In a successfully cancer gene therapy, a smart gene delivery system is necessary for both protecting the therapeutic genes in circulation and enabling high gene expression in tumor sites. Magnetic iron oxide nanoparticles (IONPs) have demonstrated their bright promise for highly efficient gene delivery target to tumor tissues, partly due to their good biocompatibility, magnetic responsiveness, and extensive functional surface modification. In this review, the latest progress in targeting cancer gene therapy is introduced, and the unique properties of IONPs contributing to the efficient delivery of therapeutic genes are summarized with detailed examples. Furthermore, the diagnosis potentials and synergistic tumor treatment capacity of IONPs are highlighted. In addition, aiming at potential risks during the gene delivery process, several strategies to improve the efficiency or reduce the potential risks of using IONPs for cancer gene therapy are introduced and addressed. The strategies and applications summarized in this review provide a general understanding for the potential applications of IONPs in cancer gene therapy.