Objective To develop a novel carrier-free spherical nanomedicine with daunorubicin(DNR)for combined chemotherapy of leukemia and systematically study its physicochemical properties,drug release behavior,and in vitro and in vivo therapeutic efficacy. Methods DNR was chemically conjugated with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine(DOPE)for the self-assembly of nanoparticles,which were further loaded with cytarabine(Ara-C)to form DOPE-DNR Ara-C nanomedicine(DDA NPs)for combined chemotherapy of acute myeloid leukemia.The particle size and surface potential of DDA NPs were characterized by dynamic light scattering and zeta potential analysis.The drug release behavior in high-concentration glutathione(GSH)was studied through reduction-responsive drug release experiments.In vitro cytotoxicity assays were conducted to evaluate the inhibitory effect on leukemia cells,while a rat model of leukemia was used to assess the antitumor efficacy in vivo. Results DDA NPs exhibited a spherical nanostructure with a particle size of(123.67±0.11)nm and the zeta potential of(-25.60±0.67)mV,showing good stability under physiological conditions.High-concentration GSH effectively triggered disulfide bond cleavage,facilitating targeted drug release.In vitro,DDA NPs significantly enhanced drug accumulation in the nuclei of LT-12 leukemia cells and improved the cytotoxicity of DNR.The animal experiment showed that compared with free drugs,DDA NPs significantly reduced the number of leukemia cells in rat bone marrow,prolonged the survival,and effectively inhibited leukemia cell infiltration while alleviating organ damage. Conclusions DDA NPs as a novel carrier-free nanomedicine significantly enhanced drug delivery efficiency and synergistic therapeutic effects.It demonstrates good clinical translation potential and may provide a new therapeutic strategy for the treatment of acute myeloid leukemia.
Kong et al. (Sun,) studied this question.