Session: 401. Blood Transfusion: Poster III
Hematology Disease Topics & Pathways:
Research, Fundamental Science
Methods:E-Dox was prepared using a hypotonic-hypertonic method. Characterization and release assays confirmed the successful preparation of E-Dox. Subsequent investigations evaluated the tumor inhibitory capacity, pharmacokinetics, and biodistribution in vivo. We also analyzed the immune environment in the bone marrow and spleen using flow cytometry and IHC staining. Furthermore, the safety profile of the system was validated.
Results:E-Dox preparation preserved the biconcave disc morphology, with minimal differences in cellular protein, notably CD47, compared to normal erythrocyte as determined by Western Blot analysis. Furthermore, the system exhibited high encapsulation efficiency, reaching 80%. E-Dox also demonstrated significant tumor inhibitory effects. Following treatment with E-Dox, there was an increase in early apoptotic cells among tumor cells and elevated production of reactive oxygen species within the tumor cells compared with free Dox. Importantly, E-Dox markedly prolonged drug half-life, achieving a four-fold extension compared to free drug formulations. Leukemia mice treated with E-Dox showed attenuated tumor progression and prolonged survival period. Interestingly, by analyzing the immune environment in the bone marrow and spleen, we observed an increase in activated T cells and cytotoxic T cells in mice treated with E-Dox. And Hepatic and renal function tests, along with histopathological analysis, indicated favorable biocompatibility of E-Dox and alleviated doxorubicin-induced cardiac toxicity.
Conclusion:This study elucidates an optimal strategy for preparing E-Dox, successfully creating an intact and functional erythrocyte-based delivery platform. The system significantly extends drug action duration, effectively suppresses leukemia in mouse models, and demonstrates biocompatibility, thereby mitigating chemotherapy-induced organ toxicity.
Disclosures: No relevant conflicts of interest to declare.