{Reference Type}: Journal Article
{Title}: A Coupling-Induced Assembly Strategy for Constructing Artificial Shell on Mitochondria in Living Cells.
{Author}: Song BL;Wang JQ;Zhang GX;Yi NB;Zhang YJ;Zhou L;Guan YH;Zhang XH;Zheng WF;Qiao ZY;Wang H;
{Journal}: Angew Chem Int Ed Engl
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jul 24
{Factor}: 16.823
{DOI}: 10.1002/anie.202411725
{Abstract}: The strategy of in vivo self-assembly has been developed for improved enrichment and long-term retention of anticancer drug in tumor tissues. However, most self-assemblies with non-covalent bonding interactions are susceptible to complex physiological environments, leading to weak stability and loss of biological function. Here, we develop a coupling-induced assembly (CIA) strategy to generate covalently crosslinked nanofibers, which is applied for in situ constructing artificial shell on mitochondria. The oxidation-responsive peptide-porphyrin conjugate P1 is synthesized, which self-assemble into nanoparticles. Under the oxidative microenvironment of mitochondria, the coupling of thiols in P1 causes the formation of dimers, which is further ordered and stacked into crosslinked nanofibers. As a result, the artificial shell is constructed on the mitochondria efficiently through multivalent cooperative interactions due to the increased binding sites. Under ultrasound (US) irradiation, the porphyrin molecules in the shell produce a large amount of reactive oxygen species (ROS) that act on the adjacent mitochondrial membrane, exhibiting ~2-fold higher antitumor activity than nanoparticles in vitro and in vivo. Therefore, the mitochondria-targeted CIA strategy provides a novel perspective on improved sonodynamic therapy (SDT) and shows potential applications in antitumor therapies.