Using Metal-Organic Framework Nanoparticles for Targeted Codelivery of Bortezomib and Iron Ions to Mitochondrial TOM20 to Induce Ferroptosis for Colorectal Cancer Treatment

Targeted promotion of iron ion accumulation and inhibition of outer membrane protein function in mitochondria contribute to Ferroptosis, thereby boosting anticolorectal Cancer (CRC) efficacy. Based on our previous study, the Anticancer agent bortezomib (BTZ) was loaded in an iron-derived metal-organic framework (MOF), which was further modified by rhodamine B (RhB), yielding BTZ@RhB-MOF for targeted CRC treatment. Physicochemical characterization results indicated successful preparation of BTZ@RhB-MOF, which had the framework structure and nanosize properties with BTZ and iron ion release under acidic conditions. Further measurements indicated that BTZ@RhB-MOF could be distributed more effectively in tumor tissues, owing to its targeted characteristics. BTZ@RhB-MOF was mainly localized at the mitochondrial outer membrane, where it bound to TOM20 and subsequently destroyed the mitochondria of CRC cells. Then, BTZ@RhB-MOF released the iron ions it was carrying, increasing the concentration of intracellular iron ions and inducing vigorous Ferroptosis. Finally, in vitro and in vivo experiments demonstrated that BTZ@RhB-MOF could suppress CRC cells and tumor grafts in CRC cell-bearing mice with favorable safety. Thus, the targeted codelivery of BTZ and iron ions using MOF to the mitochondria of CRC cells was achieved. Therefore, BTZ@RhB-MOF can effectively induce Ferroptosis by suppressing TOM20 and increasing iron ion concentrations after the agents are unloaded, offering a potentially targeted strategy for CRC chemotherapy.

TOM20; bortezomib; colorectal cancer; ferroptosis; metal−organic framework.