Affiliation:
1. CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety National Center for Nanoscience and Technology (NCNST) Beijing 100190 China
2. Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of Sciences Beijing 100049 PR China
3. Harbin Medical University Cancer Hospital No. 150 Haping Road, Nangang District Harbin 150081 China
4. NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics Heilongjiang Key Laboratory of Scientific Research in Urology Harbin Medical University Harbin 150001 China
Abstract
AbstractThe 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.