A Bifunctional Bionanoindicator for Targeted Chemotherapy and Simultaneous In Situ Monitoring of Mitochondrial Dysfunction-Induced Cytochrome c in Acute Myeloid Leukemia Cells

Targeting mitochondria to mediate tumor apoptosis is a promising approach for treating acute myeloid leukemia (AML). However, highly heterogeneous AML cell populations exhibit varying sensitivities to chemotherapeutic agents. Timely, in-situ detection of chemotherapeutic drug-induced mitochondrial dysfunction in a single leukemia cell is crucial for monitoring treatment efficacy. In this study, we develop an integrated nanoindicator that targets the delivery of the chemotherapeutic agent dihydroartemisinin to AML cells, induces mitochondrial dysfunction, and simultaneously monitors the release of the mitochondrial dysfunction related marker cytochrome c (Cyt c) in real time. A 2D MXene nanosheet is chemically modified with hyaluronic acid for AML cell targeting and loaded with dihydroartemisinin to induce mitochondrial dysfunction and Cyt c release. MXenes are paired with graphene quantum dots modified with a Cyt c recognition aptamer to construct a bionanoindicator for Cyt c. This bifunctional bionanoindicator enables the detection of mitochondrial dysfunction and Cyt c both in vitro and in vivo, demonstrating potential for drug development and personalized medicine.