Erythrocyte membrane-camouflaged DNA-functionalized upconversion nanoparticles for tumor-targeted chemotherapy and immunotherapy

摘要

A synergistic combination of treatment with immunogenic cell death(ICD)inducers and immunoadjuvants may be a practical way to boost the anticancer response and successfully induce an immune response.The use of HR@UCNPs/CpG-Apt/DOX,new biomimetic drug delivery nanoparticles generated to combat breast cancer,is reported here as a unique strategy to produce immunogenicity and boost cancer immunotherapy.HR@UCNPs/CpG-Apt/DOX(HR-UCAD)consists of two parts.The core is composed of an immunoadjuvant CpG(a toll-like receptor 9 agonist)fused with a dendritic cell-specific aptamer sequence(CpG-Apt)to decorate upconversion nanoparticles(UCNPs)with the successful intercalation of doxorubicin(DOX)into the consecutive base pairs of Apt-CpG to construct an immune nanodrug UCNPs@CpG-Apt/DOX.The targeting molecule hyaluronic acid(HA)was inserted into a red blood cell membrane(RBCm)to form the shell(HR).HR-UCAD possessed a strong capacity to specifically induce ICD.Following DOX-induced ICD of cancer cells,sufficient exposure to tumor antigens and UCNPs@CpG-Apt(UCA)activated the tumor-specific immune response and reversed the immunosuppressive tumor microenvironment.In addition,HR-UCAD has good biocompatibility and increases the active tumor-targeting effect.Furthermore,HR-UCAD exhibits excellent near-infrared upconversion luminescence emission at 804 nm under irradiation with a 980 nm laser,which has great potential in biomedical imaging.Thus,the RBCmcamouflaged drug delivery system is a promising targeted chemotherapy and immunotherapy nanocomplex that could be used for effective targeted breast cancer treatment.