Vaccination is critical for population protection from pathogenic infections. However, its efficiency is frequently compromised by a failure of antigen retention and presentation. Herein, we designed a dextran-binding protein DexBP, which is composed of the carbohydrate-binding domains of Trichoderma reesei cellobiohydrolases Cel6A and Cel7A, together with the sequence of the fluorescent protein mCherry. DexBP was further prepared by engineered Escherichia coli cells and grafted to magnetic nanoparticles. The magnetic nanoparticles were integrated with a dextran/poly(vinyl alcohol) framework and a reactive oxygen species-responsive linker, obtaining magnetic polymeric microgels for carrying pathogen antigen. Similar to amoeba aggregation, the microgels self-assembled to form aggregates and further induced dendritic cell aggregation. This step-by-step assembly retained antigens at lymph nodes, promoted antigen presentation, stimulated humoral immunity, and protected the mice from life-threatening systemic infections. This study developed a magnetic microgel-assembling platform for dynamically regulating immune response during protection of the body from dangerous infections.

Systemic infections caused by life-threatening pathogens represent one of the main factors leading to clinical death. In this study, we developed a pathogen infection-responsive and macrophage endoplasmic reticulum-targeting nanoplatform to alleviate systemic infections. The nanoplatform is composed of large-pore mesoporous silica nanoparticles (MSNs) grafted by an endoplasmic reticulum-targeting peptide, and a pathogen infection-responsive cap containing the reactive oxygen species-cleavable boronobenzyl acid linker and bovine serum albumin. The capped MSNs exhibited the capacity to high-efficiently load the antimicrobial peptide melittin, and to rapidly release the cargo triggered by H₂O₂ or the pathogen-macrophage interaction system, but had no obvious toxicity to macrophages. During the interaction with pathogenic Candida albicans cells and macrophages, the melittin-loading nanoplatform MSNE+MEL+TPB strongly inhibited pathogen growth, survived macrophages, and suppressed endoplasmic reticulum stress together with pro-inflammatory cytokine secretion. In a systemic infection model, the nanoplatform efficiently prevented kidney dysfunction, alleviated inflammatory symptoms, and protected the mice from death. This study developed a macrophage organelle-targeting nanoplatform for treatment of life-threatening systemic infections.

Owing to the stimulus-responsive and dynamic properties, magnetism-driven assembly of building blocks to form ordered structures is always a marvelous topic. While abundant magnetic assemblies have been developed in ideal physical and chemical conditions, it remains a challenge to realize magnetic assembly in complicated biological systems. Herein, we report a kind of biomacromolecule-modified magnetic nanosheets, which are mainly composed of superparamagnetic graphene oxide (γ-Fe₂O₃@GO), the tumor-targeting protein transferrin (TF), and the mitochondrion-targeting peptide (MitP). Such large-size nanosheets (0.5-1 μm), noted as L-Fe₂O₃@GO-MitP-TF, can successfully in situ assemble on the surface of tumor cells in a size-dependent and tumor cell-specific way, leading to severe inhibition of nutrient uptake for the tumor cells. More significantly, the nanostructures could efficiently confine the tumor cells, preventing both invasion and metastasis of tumor cells both in vitro and in vivo. Moreover, the 2D assemblies could remarkably disrupt the mitochondria and induce apoptosis, remarkably eradicating tumors under near-infrared (NIR) irradiation. This study sheds light on the development of new nano-systems for efficient cancer therapy and other biomedical applications.