Purpose <p>Pluronic nanoparticles (NPs) containing doxorubicin and viral epitope (DOX/viral epitope Pluronic NPs) were designed and characterized for immune-chemo combination therapy to improve therapeutic efficacy and reduce side effects.</p> Methods <p>DOX/viral epitope Pluronic NPs are composed of doxorubicin, heparin and viral epitope (LCMV GP (33–41)) and are enveloped in Pluronic F127 using Freeze drying. A transmission electron microscope (TEM) and particle size analyzer were deployed to verify the structure of the NPs. The biodistribution and antitumor efficacy of the NPs were examined with tumor bearing mice to understand enhanced antitumor efficacy. Reduced side effects were verified by observing cardiotoxicity and body weight change.</p> Results <p>The incorporation of the viral epitope into the NPs was achieved by freeze drying the aqueous media containing the nanoaggregates formed through electrostatic interaction between DOX and heparin, Pluronic F 127, and LCMV GP (33–41). Our study suggests that DOX/viral epitope Pluronic NPs can be successfully prepared and are very effective for improving antitumor efficacy with reduced side effects in immune-chemo combination therapy.</p> Conclusion <p>DOX/viral epitope Pluronic NPs showed an increased antitumor efficacy with a reduced side effect. This indicates that the NPs in this study can be utilized for the co-delivery for DOX and the LCMV GP (33–41) to demonstrate combination therapy.</p>