Negotiating in a Foreign Land : Understanding the Curious Interactions Between Intracellular Mitochondria and Internalized Nanoparticles

ABSTRACT Intracellular mitochondria are fascinating organelles that began their evolutionary journey as symbiotic α‐proteobacteria, negotiating safety and residence in (eukaryotic) cells in exchange for managing the host's energy demands. The archaic bacterium that was engulfed by cells has left its mark on modern mitochondria, including the well‐studied mitochondrial membrane, matrix, and genetic makeup. Similarly, nanoparticles, abundant in the atmosphere and inherently reactive, have interacted with life forms throughout their existence. One such multidimensional, complex reciprocity is the mitochondria‐nanoparticle interaction, which is biomedically relevant. Charged nanoparticles may disrupt the electron transport chain in the mitochondrial membrane that produces ATP, thereby depleting cells of their energy supply. Additionally, a disrupted electron transport produces excess reactive oxygen species, leading to oxidative stress, known to cause neurodegenerative, cardiovascular, and neurological diseases. However, recent advancements in nanotechnology and synthesis have uncovered novel opportunities to exploit this mitochondria‐nanoparticle interface, including theranostic possibilities via mitochondrial targeting with functionalized nanoparticles, with or without an encapsulated payload of theranostic agents such as peptides and genetic materials. This account will strive to understand the intricacies of this interface and elucidate the theranostic possibilities it offers.