Black Phosphorus Nanosheets Assist Nanoerythrosomes for Efficient Mrna Vaccine Delivery and Immune Activation

The mRNA-based vaccines have enormous potential in infectious disease prevention and tumor neoantigen application. However, developing an advanced delivery system for efficient mRNA delivery and intracellular release for protein translation remains a challenge. Herein, we design a biocompatible biomimetic system using red blood cell-derived nanoerythrosomes (NER) and black phosphorus nanosheets (BP) for mRNA delivery. The BP is covalently modified with polyethyleneimine (PEI), serving as a core to efficiently condense mRNA via electrostatic interactions. To facilitate the spleen targeting of the mRNA-loaded BP (BP mRNA ), NER is co-extruded with BP mRNA to construct a stable “core-shell” structure nanovaccine (NER@BP mRNA ). The mRNA nanovaccine exhibits efficient protein expression and immune activation via BP-mediated adjuvant effect and enhanced lysosomal escape. In vivo evaluation demonstrates that the system delivery of mRNA encoding the coronavirus receptor-binding domain (RBD) significantly increases the antibody titer and pseudovirus neutralization effect compared to that of NER without BP assistance. Furthermore, the mRNA extracted from mouse melanoma tissues is utilized to simulate tumor neoantigen delivered by the NER@BP mRNA. In the vaccinated mice, BP-assisted NER for the delivery of melanoma mRNA can induce more antibodies that specifically recognize tumor antigens. Thus, BP-assisted NER can serve as a safe and effective delivery vehicle in mRNA-based therapy. This article is protected by copyright. All rights reserved