Nanoparticles encapsulated with natural venoms have a considerable attention to improve illnesses therapies by overcoming toxic effects secreted by different pathogens. The present study explored conjugation of chitosan extracted from cuticle of naturally died honeybees nanoparticles (B-Cs-NPs) with the honeybee, Apis mellifera venom (BV). Detected related toxicity and anticancer potential of BV and BV loaded NPs- against Colon (CaCO-2), Larynx (HEp-2) and breast (MCF-7) cancer cell lines. The Inotropic gelation of chitosan (CS) with sodium tripolyphosphate (TPP) was the method used to prepare nanoparticles. Cytotoxic effects of BV and BV loaded NPs nanoparticles against the three cancer cell lines studied, then they were assessed using MTT stain assay. Data recorded revealed that combination of bee venom with bee chitosan nanoparticles enhanced the inhibitory effect against cancer cells studied when compared with bee venom alone. Also, it was cleared that by treating CaCO-2, HEp-2 & MCF-7 cell lines with IC50 concentrations of BV alone and BV loaded chitosan nanoparticles, this induced apoptotic features as cell shrinking, peripheral condensation of chromatin, apoptotic
bodies in late stage, nucleoli fragmentation, membrane blebbing, shrunken nucleus with some necrotic features. Control cells showed normal pathway of mitotic divisions of obvious cell membrane and nucleus when stained by (H&E) and by visualization using inverted microscope.