2025/10/23 by Jungryun Kim, Chong Hu, Paramesh Jangili +3
Medicine · Biochemistry, Genetics and Molecular Biology · #Pneumocystis jirovecii pneumonia detection and treatment #HIV/AIDS drug development and treatment #Cancer therapeutics and mechanisms
paper · doi:10.1021/acs.jmedchem.5c02565
Residual tumor cells that persist after chemotherapy, even in minimal quantities, often exhibit drug resistance and increased invasiveness, potentially leading to tumor metastasis and recurrence. This study introduces a novel reactive oxygen species (ROS)-responsive prodrug, Dex-Dox, designed to overcome multidrug resistance (MDR) in tumor cells. The prodrug is composed of the anti-inflammatory glucocorticoid dexamethasone (Dex) conjugated with doxorubicin (Dox), a widely used antitumor agent, through an oxidative stress-responsive linker. Our in vitro findings revealed that, while Dex alone did not exhibit antitumor activity, Dex-Dox significantly enhanced drug sensitivity, promoting apoptosis and inhibiting angiogenesis in drug-resistant cells. Furthermore, in vivo therapeutic evaluations and histological analyses demonstrated that Dex-Dox substantially reduced tumor volumes, especially in a Dox-resistant tumor mouse model, underscoring its potential as an effective strategy against MDR in cancer therapy.