Work

The trojan horse strategy in T-ALL therapy by engineering T-ALL-derived exosomes for targeted delivery of Isoliquiritigenin to the bone marrow to conquer Drug-Resistant T-ALL in PDX model

Year: 2025

Type: article

Abstract: T-cell acute lymphoblastic leukemia (T-ALL) is often associated with poor prognosis due to high rates of drug resistance and relapse. In this study, the researchers developed a Trojan horse nanotherapeutic strategy that leverages exosomes produced by T-ALL cells to deliver Isoliquiritigenin (ISL) to conquer drug resistant T-ALL. This innovative exosomal drug delivery platform, derived from T-ALL resistant cell lines, is recognized and absorbed by leukemia cells in vivo , enabling targeted enrichment in the bone marrow. Consequently, it facilitates the delivery and release of ISL (the ’soldier’), aiming to enhance therapeutic selectivity and overcome drug resistance. The anticancer effects of ISL and exosome-encapsulated ISL (Exo-ISL) on drug-resistant T-ALL cells were evaluated through biological assays, cell line-derived xenograft (CDX), and patient-derived xenograft (PDX) models. To elucidate the underlying mechanisms, RNA sequencing, acridine orange staining, comet assays, and γ-H2AX immunofluorescence were performed. Our findings demonstrate that T-ALL-derived exosomes significantly enhance the targeted delivery of ISL to the bone marrow. Furthermore, ISL’s effects on drug-resistant T-ALL have been found to involve multiple mechanisms, including induction of apoptosis, DNA damage, and autophagy.

Source: Chemical Engineering Journal

DOI: 10.1016/j.cej.2025.159379