We have fabricated a novel method to achieve therapy- triggered changes in tumor cells by using promising effects concerning dual chemotherapeutic drugs. Dual-drug conveyance of Salinomycin (SAL) and Doxorubicin (DOX) exhibits a great anti-tumor ability, as SAL improves the impact of DOX management of glioma cells by supplying stability of the microenvironment. Nevertheless, encapsulations of SAL and DOX fanatical by (lactic-co-glycolic acid (PLGA) and polyethylene glycol (PEG)- based nanoparticles (NPs) is incompetents due to inappropriateness between the dual drug SAL and DOX polymeric framework. At the present, we show DOX and SAL can be formulated with dioleoylphosphatide acid (DOPA) through the hydrophobic covering of drug centers. In PEG-PLGA NPs, the DOPA- enclosed DOX can be co-incorporating in addition to SAL to encourage superior cancer activities. The DOX revealed seductively that the SAL encapsulations in PEG-PLGA NPs (SAL-DOX NPs) were improved. The transmission microscopy (TEM) studied the morphology of SAL NPs, DOX NPs, SAL-DOX NPs, and nanoparticle size. SAL-DOX NPs also induced major apoptosis in vitro human glioma cells such as LN229 and U251. Different biochemical trials such as AO-EB, Hoechst staining, and annexin V-FITC have confirmed morphological observations and apoptosis. The findings indicate that the SAL-DOX NPs is one of the promising caregivers of therapeutic candidates for human glioma cancer worth further study.