Tobacco addiction has consistently been the top preventable cause of many serious diseases, and results in huge mortality, morbidity, and economic loss in recent decades. Despite the strong willingness to quit smoking, most of the smokers cannot achieve long term abstinence without medical interventions. However, current FDA approved pharmacological therapies only show very limited success. Currently, nicotine vaccine that can induce nicotine specific antibodies is considered as a promising approach against tobacco addiction. However, traditional protein-hapten conjugate nicotine vaccines have shown less than desired immunological efficacy due to their poor recognition and internalization by immune cells. The lipid-polymeric hybrid nanoparticle based nicotine vaccine developed in this invention could help to overcome those limitations. Our current experimental results indicated that the nicotine nanovaccine could induce significantly higher antibody titer than conjugate nicotine vaccine, which could considerable enhance the immunogenicity over traditional conjugate nicotine vaccines. In addition, by modulating nanovaccine particle size, up to around 60% of the administrated nicotine could be blocked from entering brain. Moreover, PLGA and liposome are two FDA approved safe materials which can be used in human. As expected, our safety experiments demonstrated that no apparent toxicity of the nanovaccine was detected. Based on those results, this lipid-polymeric hybrid nanoparticle based nicotine vaccine can be a promising candidate for treating nicotine dependence.