Cells can take up mitochondria from the surrounding environment, and researchers have demonstrated in mice that intravenous delivery of mitochondria allows some degree of replacement of the native populations in cells. This improves function when native mitochondria are dysfunctional, as occurs with age. At present, delivery of mitochondria as a therapy to restore mitochondrial function in older people is a work in progress. A few companies are working on the challenge, which largely involves developing the techniques needed to reliably manufacture mitochondria at scale. In this paper, researchers look beyond that effort to the next step in the road, which is to engineer the delivered mitochondria to be more efficient and more resilient, or to act as factories for therapeutic molecules, or to have some other desired capability.
Conventional mitochondrial transplantation (MT), a therapeutic process involving the isolation and delivery of healthy exogenous mitochondria to damaged cells or organs to restore bioenergetics and promote repair, typically relies on the direct injection or infusion of isolated, unmodified mitochondria. Inspired by cell surface engineering, we propose nanoengineered mitochondria, which are biohybrid systems formed by integrating synthetic nanomaterials or biomolecules with isolated mitochondria to confer new functionalities.
This emerging strategy operates at the interface of bioengineering and mitochondrial biology and aims to overcome the limitations of conventional MT. These tailored nanobiohybrid systems have the potential to improve mitochondrial quality, boost metabolic activity, and reduce oxidative stress. Moreover, these systems can enhance the targeting efficiency and motility of mitochondria, which is achieved through mitochondrial ligand-receptor recognition (e.g., triphenylphosphonium cation (TPP+)-modified nanoparticles and mitochondrial membrane potentials), stimulus-responsive navigation (e.g., pH/ROS-sensitive polymers guiding mitochondria to inflammatory sites), and external field-driven propulsion (e.g., magnetically steered nanocapsules). This mini-review therefore focuses specifically on the emerging of nanoengineered mitochondria, moving beyond the scope of earlier reviews that centered primarily on conventional transplantation. We envision nanoengineered mitochondria as a next-generation platform for precise anti-aging interventions.
Link: https://doi.org/10.3389/fragi.2025.1688482
View the full article at FightAging
