Nasopharyngeal carcinoma (NPC) is a serious and highly invasive epithelial malignancy that is closely associated with Epstein‒Barr virus (EBV). Due to the lack of therapeutic vaccines for NPC, we selected EBV latent membrane protein 2 (LMP2) as a preferable targeting antigen to develop a lipid-based LMP2-mRNA (mLMP2) vaccine. Full-length mLMP2 expressing LMP2 was first synthesized using an in vitro transcription method and then encapsulated into (2,3-dioleacyl propyl) trimethylammonium chloride (DOTAP)-based cationic liposomes to obtain the mRNA vaccine (LPX-mLMP2). The cell assays showed that the antigen-presenting cells were capable of highly efficient uptake of LPX-mLMP2 and expression of LMP2. LMP2 could subsequently be presented to form the peptide-major histocompatibility complex (pMHC). Furthermore, LPX-mLMP2 could accumulate in the spleen, express antigens, promote the maturation of dendritic cells and stimulate antigen-specific T-cell responses in vivo. It dramatically inhibited the tumor growth of the LMP2-expressing tumor model after three doses of vaccination. Additionally, the proliferation of antigen-specific T cells in the tumor site made a good sign for the promise of mRNA vaccines in virus-induced cancer. Overall, we provided a newly developed antigen-encoding mRNA vaccine with advantages against NPC. We also demonstrated that mRNA vaccines are attractive candidates for cancer immunotherapy.

Atherosclerosis is the main cause of ischemic stroke and myocardial infarction diseases. Nanoparticles have shown unique benefits for atherosclerosis treatment by targeting the lesional macrophages of plaques. However, most of the nanocarriers are administered intravenously, which is inconvenient and may cause complications. Herein, we developed an oral lipid-polymer based nanoparticles (FA-LNPs) decorated with folic acid, which can not only effectively overcome intestinal mucosal-epithelial barrier by increasing the transmembrane transport through intestinal epithelial and the accumulation in Peyer’s patches but also actively target to the aortic plaque sites and accumulate in lesional macrophages. Subsequently, naringenin (Nrg), one of the anti-inflammation drugs, was designed to be the oral nanomedicine (FA-LNPs/Nrg) for the first time via the encapsulation of FA-LNPs. FA-LNPs/Nrg presented highly anti-atherosclerotic efficacy. After the atherosclerotic ApoE^−/− mice were treated by FA-LNPs/Nrg via oral administration for three months, the aortic lesion area, plaque area, and necrotic core area of the aortic root were significantly decreased. Meanwhile, the lipid-related blood parameters recovered to normal levels. Our study provides a promising approach to atherosclerosis treatment based on the novel oral targeting delivery system.