Injectable etoposide-loaded dextran nanoparticles for ‎breast cancer treatment: physicochemical characterization, cytotoxicity ‎studies, macrophage activity, and gene expression profiling.

[AIM] This study aimed to develop and characterize injectable etoposide-loaded dextran sulfate sodium nanoparticles (ETP-DNPs).

[METHODS] ETP-DNPs were prepared by ionic gelation and characterized. In vitro drug release was studied for 8 h, cytotoxicity was assessed in MCF-7 breast cancer cells, macrophage activation was analyzed using IL-6 stimulation, and apoptosis-related gene expression (Bax, p53, and BCL-2) was evaluated by qRT-PCR.

[RESULTS] ETP-DNPs exhibited excellent electrostatic stability (zeta potential -33.2 ± 8.21 mV), a Z-average size of 13.03 nm, predominant particle size of 9.5 ± 3.14 nm, and a PDI of 0.314. SEM confirmed uniform spherical morphology. DSC revealed endothermic peaks between 133.5-185.2°C and an exothermic peak at 210.9°C, while TGA indicated major degradation at 286.9°C. Raman spectra showed sulfate - glycosidic interactions, and XRD peaks indicated partial crystallinity. Drug loading and encapsulation efficiency were high (83.3% and 84.6%). Drug release reached 73.45% with near zero-order kinetics. MCF-7 viability decreased dose- and time-dependently, and IL-6 assays confirmed M1 activation. ETP-DNP treatment markedly inhibited MCF-7 cell migration in a scratch assay, with minimal wound closure observed up to 48 h compared with untreated controls, indicating reduced migratory potential. In parallel, ETP-DNPs induced apoptosis by significantly upregulating Bax and increasing the Bax/BCL2 ratio, confirming activation of the intrinsic mitochondrial apoptotic pathway.

[CONCLUSION] The research findings validate ETP-DNP as a promising nanocarrier system for ‎breast cancer. ‎.