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

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 RBCm-camouflaged drug delivery system is a promising targeted chemotherapy and immunotherapy nanocomplex that could be used for effective targeted breast cancer treatment. We report the new biomimetic nanoparticles, which is the synergistic combination of immunogenic cell death inducer and immunoadjuvant, proving to be the unique strategy to successfully induce an immune response and boost the anticancer response.