Co-encapsulation of l-asparaginase and etoposide in dextran nanoparticles for synergistic effect in chronic myeloid leukemia cells

Co-encapsulation of multiple therapeutic drugs in a single nanocarrier has the potential to enable synergistic interactions, increase drug efficacy, and reduce side effects. The enzyme l-asparaginase and the small molecule drug etoposide have a known synergistic effect against selected cancer types. However, both drugs differ significantly in size, molecular weight, and solubility, which often results in challenges when a simultaneous delivery is required. In this study, we present the co-encapsulation of a large hydrophilic enzyme l-asparaginase and the small hydrophobic drug etoposide into a biodegradable, biocompatible, and acid-responsive dextran-based nanoparticle system. These dual drug-loaded nanoparticles show an excellent cellular uptake in chronic myeloid leukemia (CML) K562 cells and a stepwise release of the cytotoxic payloads in a pH-dependent manner. In activity tests, the dual drug-loaded formulation has shown a significant effect on cell viability (down to 31%) compared to those incubated only with l-asparaginase (92%) or etoposide (82%) at a particle concentration of 125 μg∙mL^-1. These results show that the simultaneous co-delivery of these two drugs in K562 cells leads to synergistic cytotoxicity, indicating a great potential for the treatment of CML.